Receptor-mediated cargo hitchhiking on bulk autophagy.

While the molecular mechanism of autophagy is well studied, the cargoes delivered by autophagy remain incompletely characterized. To examine the selectivity of autophagy cargo, we conducted proteomics on isolated yeast autophagic bodies, which are intermediate structures in the autophagy process. We identify a protein, Hab1, that is highly preferentially delivered to vacuoles. The N-terminal 42 amino acid region of Hab1 contains an amphipathic helix and an Atg8-family interacting motif, both of which are necessary and sufficient for the preferential delivery of Hab1 by autophagy. We find that fusion of this region with a cytosolic protein results in preferential delivery of this protein to the vacuole. Furthermore, attachment of this region to an organelle allows for autophagic delivery in a manner independent of canonical autophagy receptor or scaffold proteins. We propose a novel mode of selective autophagy in which a receptor, in this case Hab1, binds directly to forming isolation membranes during bulk autophagy.

Effect of oral intake initiation-establishment interval on hospital stay after oral cancer surgery.

OBJECTIVES: To clarify the effect of the period between initiation of oral intake (IOI) and establishment of oral intake (EOI) on length of hospital stay. METHODS: This retrospective study included postoperative oral cancer patients. The number of days from surgery to IOI and EOI and between IOI and EOI were recorded. We performed intergroup comparisons and Cox regression analysis using the number of days until discharge, representing hospital stay length as the dependent variable. RESULTS: The median number of days between IOI and EOI was 3 days for eligible patients and 4.5 and 1.5 for older and younger patients, respectively. The median number of days from surgery to IOI was 15 days. There was a significant correlation between the period between IOI and EOI and the length of hospital stay (r = 0.40, p < 0.01). The period between IOI and EOI was a significant independent variable for the length of hospital stay (HR [95% confidence interval] = 0.45 [0.28-0.72]). CONCLUSIONS: Shortening the IOI to EOI intervals was identified as an independently associated factor for shortening hospital stay, even in older postoperative patients with dysphagia who struggled with early oral intake initiation. Professional, step-by-step dysphagia rehabilitation tailored to the patient's condition yields beneficial outcomes.

Clinicopathological analysis of 134 patients with squamous cell carcinoma of the mandibular gingiva.

Objective: The accurate assessment of the involvement of mandibular gingival squamous cell carcinoma (SCC) is essential for determining the extent of resection and is also useful for predicting lymph node metastasis and prognosis. The purpose of this study was to investigate the factors for predicting the prognosis. Study design: We reviewed 134 patients with mandibular gingival SCC treated between 2008 and 2017. The clinical findings, TN stage, relationship between radiographical type and histological pattern, and factors affecting the survival rate were investigated. Results: The moth-eaten radiographic type was significantly associated with histologically infiltrative pattern. For all 134 cases, the 5-year OS was 89.5 %, and 5-year DSS was 93.9 %. The 5-year DSS was 95.0 % for cN0 and/or pN0 cases and 90.3 % for pN (+) cases, with a significant difference. The significant risk factors for lymph node metastasis were teeth extractions by previous physicians and moth-eaten radiographic type. Conclusion: The risk factor for poor prognosis was lymph node metastasis. In addition, teeth extractions by previous physicians and moth-eaten radiographic type were the risk factors for lymph node metastasis. It is recommended that these cases be treated considering the possibility of cervical lymph node metastasis.

Invasion of the bucco-mandibular space by oral squamous cell carcinoma: histopathological analysis of invasion pattern.

Background: This study aimed to determine the patterns of invasion of oral squamous cell carcinoma (OSCC) into the bucco-mandibular space (BMS) using detailed histopathological analysis and to assess clinical outcomes. Methods: Patients with OSCC who underwent segmental mandibulectomy or hemi-mandibulectomy combined with resection of the BMS between 2012 and 2021 were included. The invasions of the BMS were classified into three patterns. Pattern A was defined as a horizontal invasion, Pattern B as a vertical invasion, and Pattern C as an expansive invasion. Results: In total, 109 patients were reviewed. Of these 109 patients, the primary tumor affected the lower gingiva in 78 patients, the buccal mucosa in 18 patients, and was a primary intraosseous carcinoma of the mandible in 13 patients. Invasion of the BMS was significantly associated with a higher pathological T stage, positive/close margins, and lower disease-free survival (DFS) rates. The DFS rates were 86.7% and 66.0% in the BMS non-invasion and invasion groups, respectively. The DFS rates for each type of invasion were 82.1% for Pattern A, 67.4% for Pattern B, and 48.0% for Pattern C (P=0.277). Conclusion: Patients with BMS invasion have a poorer prognosis than those without invasion of the BMS. Therefore, adjuvant therapy is necessary, especially in Patterns B and C. Evaluation of preoperative BMS invasion patterns is important for predicting the prognosis of OSCC.

A case of sclerosing odontogenic carcinoma of the mandible with a review of the literature.

Sclerosing odontogenic carcinoma (SOC) is a very rare malignant odontogenic tumor characterized by sclerotic stroma and single-file cord-like tumor cell structures. A 38-year-old man presented with extraoral swelling and right mental region paralysis. Panoramic radiography revealed an ill-defined radiolucent lesion extending from the right mandibular ramus to the right lower canine. Magnetic resonance imaging showed tumor invasion into the right inferior alveolar nerve and masseter muscle. Hemimandibulectomy, bilateral neck dissection, and mandibular reconstruction were performed using a rectus abdominis musculocutaneous flap and a titanium plate. Histopathology and immunohistochemistry confirmed SOC diagnosis. No recurrence occurred in the 1-year follow-up. In this paper, a case of SOC with a high Ki-67 labeling index was reported. Since SOC is prone to nerve invasion, treatment is resection with an appropriate surgical margin.

Buccinator muscle invasion is a risk factor for cervical lymph node metastasis in squamous cell carcinoma of the buccal mucosa: A retrospective study.

The present study aimed to determine the risk factors associated with cervical lymph node metastasis (CLNM) in patients with buccal mucosa squamous cell carcinoma (BMSCC). This retrospective study included patients with primary BMSCC who underwent surgery at the Department of Oral and Maxillofacial Surgical Oncology of Tokyo Medical and Dental University (Tokyo, Japan) between January 2008 and December 2017. The following data were collected and analyzed: Sex, age, primary lesion subsite, tumor/node/metastasis stage, clinical growth patterns, tumor differentiation, lymphovascular and perineural invasion, mode of invasion, pathological depth of invasion, extent of tumor invasion, and clinical outcome of patients with BMSCC. Multivariate analysis was performed to identify the possible risk factors for CLNM. A total of 75 patients were included in the present study, among whom 30 (40%) were found to have histological CLNM. Of the 33 patients with buccinator muscle infiltration by the tumor, 24 (72.7%) had CLNM. Multiple logistic regression analysis revealed that buccinator muscle invasion was the most significant predictive risk factor for CLNM in BMSCC. The present study found that tumor invasion of the buccinator muscle was the most significant predictive risk factor for CLNM in BMSCC. Therefore, elective neck dissection should be performed if buccinator muscle invasion is identified in patients with BMSCC.

Bur1 functions with TORC1 for vacuole-mediated cell cycle progression.

The vacuole/lysosome plays essential roles in the growth and proliferation of many eukaryotic cells via the activation of target of rapamycin complex 1 (TORC1). Moreover, the yeast vacuole/lysosome is necessary for progression of the cell division cycle, in part via signaling through the TORC1 pathway. Here, we show that an essential cyclin-dependent kinase, Bur1, plays a critical role in cell cycle progression in cooperation with TORC1. A mutation in BUR1 combined with a defect in vacuole inheritance shows a synthetic growth defect. Importantly, the double mutant, as well as a bur1-267 mutant on its own, has a severe defect in cell cycle progression from G1 phase. In further support that BUR1 functions with TORC1, mutation of bur1 alone results in high sensitivity to rapamycin, a TORC1 inhibitor. Mechanistic insight for Bur1 function comes from the findings that Bur1 directly phosphorylates Sch9, a target of TORC1, and that both Bur1 and TORC1 are required for the activation of Sch9. Together, these discoveries suggest that multiple signals converge on Sch9 to promote cell cycle progression.

Clinical manifestations of diffuse large B-cell lymphoma that exhibits initial symptoms in the maxilla and mandible: a single-center retrospective study.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphatic tumor; however, extranodal DLBCLs that exhibit initial symptoms in the maxilla and mandible are rare. Moreover, DLBCL is clinically classified as a moderate to highly malignant lymphatic tumor that can progress rapidly; therefore, early diagnosis is crucial. However, diagnosis is difficult as the disease causes a diverse range of clinical symptoms with no characteristic imaging findings. We conducted a clinical investigation to clarify the clinical characteristics of DLBCL that exhibits initial manifestation in the maxilla and mandible. METHODS: Of the 2748 patients with malignant tumors of the oral and maxillofacial region examined at our hospital during a period of 11 years between January 2006 and December 2016, 27 primary cases diagnosed with DLBCL based on the chief complaint of symptoms in the gingiva and bone of the maxilla and mandible were enrolled in this study. Evaluations were based on sex, age, whether treatment was provided by a previous physician, symptoms, duration of disease until treatment was sought, clinical diagnosis, laboratory findings, and imaging results. RESULTS: There were 15 cases that involved the maxilla and 12 that involved the mandible. The median duration of disease until treatment was sought was 60 d (3-450 d). All cases exhibited a tumor or a mass, and hypoesthesia of the chin was confirmed in eight cases wherein the mandible was involved. The clinical stages were stage I in eight cases, stage II in ten cases, and stage IV in nine cases. Serum lactate dehydrogenase (LDH) levels were elevated in 13 of 22 patients. The overall survival rate was 63%. CONCLUSIONS: Symptoms associated with nontender swelling and numbness of the lip or chin in the absence of other findings such as dental infections should raise suspicions about DLBCL. Patients should be provided appropriate imaging and accurate biopsy assessments to improve prognosis.

MRI before biopsy correlates with depth of invasion corrected for shrinkage rate of the histopathological specimen in tongue carcinoma.

The purpose of this study was to evaluate which radiological depth of invasion (r-DOI) measurement is the most concordant to clinical DOI (c-DOI) derived from correction for the shrinkage rate of the histopathological specimens. We retrospectively reviewed 128 patients with tongue carcinoma who had undergone glossectomy between 2006 and 2019. At first, the width shrinkage rate during formalin fixation and preparation process of histopathological specimens was evaluated. From the shrinking rates, a formula to calculate c-DOI from pathological DOI (p-DOI) was developed. The correlation between c-DOI and r-DOI was evaluated. The specimen shrinkage rate during the histopathological specimen preparation process was 10.3%. Based on that, we yielded the correct formula for c-DOI based on p-DOI and preparation shrinkage rate: c-DOI = p-DOI × 100/89.7. The regression equations for the association of c-DOI with r-DOI measured by ultrasound (n = 128), MRI before biopsy (n = 18), and MRI after biopsy (n = 110) were y = 1.12 * x + 0.21, y = 0.89 * x - 0.26, and y = 0.52 * x + 2.63, respectively, while the coefficients of determination were 0.664, 0.891, and 0.422, respectively. In conclusion, r-DOI using MRI before biopsy most strongly correlated with c-DOI.

Prognostic impact of lingual lymph node metastasis in patients with squamous cell carcinoma of the tongue: a retrospective study.

Squamous cell carcinoma (SCC) of the tongue rarely metastasizes to the lingual lymph nodes (LLNs), which are inconstant nodes and often situated outside the areas of basic tongue tumor surgery. The current study evaluated the clinicopathological features and prognostic impact of LLN metastasis (LLNM), compared to that of cervical lymph node metastasis, in patients with tongue SCC. A total of 608 patients underwent radical surgery for tongue SCC at our department between January 2001 and December 2016. During neck dissection, we scrutinized and resected lateral LLNs, when present. Of the 128 patients with lymph node metastasis, 107 had cervical lymph node metastasis and 21 had both cervical lymph node metastasis and LLNM. Univariate analysis demonstrated that LLNM was significantly associated with the adverse features of cervical lymph node metastasis. The 5-year disease-specific survival (5y-DSS) was significantly lower in patients with LLNMs than in those without LLNMs (49.0% vs. 88.4%, P < 0.01). Moreover, Cox proportional hazards model analyses revealed that cervical lymph node metastasis at level IV or V and LLNM were independent prognostic factors for 5y-DSS. LLNM has a strong negative impact on survival in patients with tongue SCC. An advanced status of cervical lymph node metastasis may predict LLNM.

Metastatic tumors in the oral region: a retrospective chart review of clinical characteristics and prognosis.

OBJECTIVE: The study aimed to evaluate the clinical characteristics and outcomes of patients with metastatic tumors in the oral region. STUDY DESIGN: We conducted a retrospective study of 14 patients (11 men and 3 women; median age, 70.5 years) with metastatic tumors in the oral region diagnosed between 2005 and 2018. RESULTS: The primary tumors were located in the lung (n = 7), kidney (n = 3), renal pelvis (n = 1), thyroid (n = 1), stomach (n = 1), and bladder (n = 1). The most common histologic type of the tumor was adenocarcinoma (n = 6). The metastatic sites were the mandible (n = 7), tongue (n = 4), upper gingiva (n = 2), and maxilla (n = 1). In 6 patients, metastatic tumors were found in the oral region before the primary tumors were detected. The primary tumors were detected by positron emission tomography/computed tomography in 5 patients and by computed tomography alone in one patient. Seven patients received treatment for metastatic tumors in the oral region. The overall 1- and 5-year survival rates were 35.7% and 10.7%, respectively. CONCLUSIONS: It is important to detect metastatic tumors in the oral region and primary tumors as early as possible. Radical or palliative treatment should be performed if possible, considering the condition of the primary tumor and its metastasis to other organs.

Mandibular Reconstruction with Scapular Systems: A Single-Center Case Series Involving 208 Flaps.

BACKGROUND: The scapular flap is the most versatile composite flap used for mandibular reconstruction. The purpose of this study was to review and summarize findings of cases of mandibular reconstruction with a scapular flap and describe associated outcomes and complications. METHODS: A total of 208 microvascular scapular free flaps were performed for mandibular reconstruction in a total of 205 patients from 2003 to 2018. This study involved a retrospective review of all eligible patients' medical records. RESULTS: There were seven cases (3.4 percent) of microvascular thrombosis. Postoperative bone union was achieved by 201 patients, except for five with total flap necrosis and two with partial flap necrosis. There were four cases (1.9 percent) of mandibular condyle dislocation. Two major types of complications were observed at the donor site, including four cases of infection and six cases of scapular body fracture. Postoperative denture prosthesis was introduced to 97 patients (47.3 percent). Implant treatment was performed in 10 patients (4.9 percent). Functional and aesthetic outcomes were good to excellent. CONCLUSIONS: The scapular composite free flap for mandibular reconstruction was associated with favorable outcomes and demonstrated satisfactory results. Although scapular bone fracture is rare, patients who have undergone mandibular reconstruction using a scapular flap should be monitored for its presence. . CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Surgical treatment for oral tongue squamous cell carcinoma: A retrospective study of 432 patients.

The incidence of oral cancer in Japan accounts for 1% of all cancers, with oral tongue cancer accounting for 60% of oral cancers based on the subsite. The most common histologic type is squamous cell carcinoma. This study aimed to evaluate the series of surgical treatments for 432 patients with oral tongue squamous cell carcinoma (OTSCC). Initial surgical treatments for the primary site included partial glossectomy, hemiglossectomy, and total or subtotal glossectomy in 348, 58, and 26 patients, respectively. Therapeutic neck dissection, elective neck dissection, and subsequent neck dissection were performed in 74, 53, and 37 patients, respectively. Patients with advanced cases had level IIb, IV, and V metastasis and outside regional lymph node metastases. The cumulative 5-year disease-specific survival rate for OTSCC was 92.8%, and the rates for each stage were 96.6%, 93.9%, 84.1%, and 79.0% in stages I, II, III, and IV, respectively. The recurrence rate, overall salvage rate for recurrent cases, and rate for the additional surgical group were 10.4%, 46.7%, and 78.6%, respectively. Patients with multiple cervical lymph node metastases, extranodal extension, metastases to multiple levels, and lower neck metastases had poor prognosis. In conclusion, careful follow-up is necessary to detect recurrence of primary tumors at a stage when surgical treatment can be performed, and cervical lymph node status is one of the most important prognostic factors in OTSCC.

Comparison of Clinicopathological Characteristics Between the Anterior and Posterior Type of Squamous Cell Carcinoma of the Floor of the Mouth: The Anterior Type Is a Risk Factor for Multiple Primary Cancer.

BACKGROUND: Floor of the mouth (FOM) squamous cell carcinoma (SCC) accounts for approximately 10% of all oral SCCs. FOM SCC can be classified into the anterior and posterior types according to their site of origin, but few studies have compared these types. This study sought to clarify differences in clinicopathological characteristics between these two types. METHODS: A total of 1,220 patients with oral SCC were treated at our department from January 2001 to December 2015. Among these patients, 62 had FOM SCC. The FOM SCCs were classified into two groups: the anterior type and the posterior type. The anterior and posterior types were defined by the boundary connecting the spaces between the canine and the first premolar bilaterally. We retrospectively compared the sex, age, smoking and drinking history, clinical stage, treatment, histopathological diagnosis, multiple primary cancers, and outcomes of the two groups. RESULTS: Among the 62 patients, 32 had the anterior type, while 30 had the posterior type. The anterior type was found more significantly in men (p = 0.01) and individuals with a smoking history than the posterior type (p = 0.04). pN2-3 cervical lymph node metastasis was significantly more common in the anterior type than in the posterior type (p = 0.01). The median depth of invasion in the anterior type was 4 mm. Multivariate analysis showed that the anterior type was an independent risk factor for multiple primary cancer development in FOM SCC (p = 0.02). The cumulative 10-year disease-specific survival rates of the anterior and posterior types were 92.8 and 95.0%, respectively, while the overall survival rates were 65.4 and 95.0%, respectively. In the anterior type FOM SCC, a lower overall survival rate was associated with multiple primary cancers and smoking-related diseases. CONCLUSION: Smoking cessation and adequate systemic screening for multiple primary cancers are needed to improve the prognosis of FOM SCC, particularly the anterior type.

DNAJA1 promotes cancer metastasis through interaction with mutant p53.

Accumulation of mutant p53 (mutp53) is crucial for its oncogenic gain of function activity. DNAJA1, a member of J-domain containing proteins or heat shock protein 40, is shown to prevent unfolded mutp53 from proteasomal degradation. However, the biological function of DNAJA1 remains largely unknown. Here we show that DNAJA1 promotes tumor metastasis by accumulating unfolded mutp53. Levels of DNAJA1 in head and neck squamous cell carcinoma (HNSCC) tissues were higher than those in normal tissues. Knockdown of DNAJA1 in HNSCC cell lines carrying unfolded mutp53 significantly decreased the levels of mutp53, filopodia/lamellipodia formation, migratory potential, and active forms of CDC42/RAC1, which were not observed in HNSCC cells with DNA contact mutp53, wild-type p53, or p53 null. Such mutp53-dependent functions of DNAJA1 were supported by the observation that DNAJA1 selectively bound to unfolded mutp53. Moreover, DNAJA1 knockdown in HNSCC cells carrying unfolded mutp53 inhibited primary tumor growth and metastases to the lymph nodes and lungs. Our study suggests that DNAJA1 promotes HNSCC metastasis mainly in a manner dependent on mutp53 status, suggesting DNAJA1 as a potential therapeutic target for HNSCC harboring unfolded mutp53.

Malignant transformation of oral lichen planus: a retrospective study of 565 Japanese patients.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory oral mucosa disease that is recognized as an oral potentially malignant disorder. However, the potentially malignant nature of OLP remains unclear. METHODS: We designed this study to examine the demographic and clinical characteristics of patients with OLP and evaluate the associated malignant transformation rate. A total of 565 patients with a clinical and histopathological diagnosis of OLP who presented at our department between 2001 and 2017 were retrospectively studied. Patients who had clinical and histopathological features of oral lichenoid lesions (OLLs) classified as oral lichenoid contact lesions, oral lichenoid drug reactions and oral lichenoid lesions of graft-versus-host disease were excluded. RESULTS: The study population included 123 men and 442 women aged 21-93 years (mean ± standard deviation, 60.5 ± 11.8). The 565 patients were followed up for a duration of 55.9 ± 45.3 months, during which 4 (0.7%) patients developed squamous cell carcinoma (SCC). In three of these 4 patients who developed SCC, the clinical type of OLP was the red type. CONCLUSIONS: Our results suggested that OLP was associated with a low risk of malignant transformation. We recommend regular follow-up for OLP patients and clear differentiation of oral epithelial dysplasia and OLLs to enable early detection of malignant transformation. Further investigation of the clinical risk factors associated with malignant transformation is necessary.

Risk factors for distant metastasis in locoregionally controlled oral squamous cell carcinoma: a retrospective study.

The control of distant metastasis in oral squamous cell carcinoma is an important determinant of improved prognosis. The study aimed to identify risk factors for distant metastasis in patients with locoregionally controlled oral carcinoma. We identified 982 patients with oral squamous cell carcinoma treated at our hospital between January 2008 and December 2017. After excluding patients with distant metastasis at initial treatment, patients with metastasis to the oral cavity, those receiving palliative treatment, and those lacking follow-up data, 941 patients were selected. Finally, among these 941 patients, 887 with locoregionally controlled oral squamous cell carcinoma were included in the study. Among the 887 patients, 36 had confirmed distant metastasis (4.1%), and the lung was the most common site (31/36 patients, 86.1%). Multivariate analysis showed that the incidence of primary intraosseous carcinoma of the mandible, cervical lymph node metastasis at levels IV and V, and the presence of pathological extranodal extension were significant risk factors for distant metastasis. When treating patients with oral squamous cell carcinoma who are positive for the aforementioned risk factors, the possibility of developing distant metastases must be accounted for, and aggressive treatment should be planned accordingly.

Postoperative morphological changes over time of vascularized scapular bone used for mandibular reconstruction: A retrospective cohort study.

BACKGROUND: Currently, sequential morphological changes of vascularized scapular bone for mandibular reconstruction have remained unreported. METHODS: We retrospectively analyzed 18 patients with defects on the lateral segment of the mandible who underwent postoperative computed tomography (CT) scanning at 1, 6, 12, and 24 months postoperatively. Using the cross-sectional coronal CT images during each assessment, we measured the height and thickness of the grafted scapular bone at points 10 and 30 mm away from the mesial segment and evaluated their differences over time. Then, the relationship between the morphological changes of the grafted scapular bone and the distance from the mesial bone segment, the number of occlusal supports on the contralateral side of the mandible, and the correlation of sex and age were evaluated. RESULTS: The height of the grafted scapular bone decreased by approximately 11% and its thickness increased by 14% within 24 months postoperatively. The bone thickness increase was greater at point 30 mm from the mesial bone segment. Patients with two occlusal contacts (premolar and molar) on the contralateral side had a significantly higher rate of bone thickness increase. Furthermore, the graft morphology was not associated with age or sex. CONCLUSION: A vascularized scapular bone thickens over time, which depends on the distance from the mesial bone segment and the occlusal contact regions on the contralateral side of the mandible.

Clinicopathological and immunohistochemical characteristics of pigmented oral squamous cell carcinoma.

Pigmented oral squamous cell carcinoma (POSCC) is a rare and underrecognized pathological variant of oral squamous cell carcinoma (OSCC). The current study aimed to evaluate the clinicopathological characteristics, treatment outcomes and prognosis of patients with POSCC and to investigate its oncological properties using immunohistochemical studies. A total of 1,512 patients were pathologically diagnosed with squamous cell carcinoma of the oral cavity, and were treated at the Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University between January 2001 and December 2018. A total of 25 patients had POSCC and underwent radical surgery. Of these 25 patients, 23 presented with early T stage disease. Additionally, 22 patients were negative for cervical lymph nodes metastasis. Only one patient had local recurrence. The 5-year disease-free and disease-specific survival rates were 86.6 and 95.8%, respectively. Immunohistochemically, a high percentage of POSCC exhibited low p53 and Ki-67, preserved E-cadherin or negative vimentin expression. The results suggested that POSCC tends to exhibit non-aggressive oncological behavior and demonstrates a good prognosis.

Vacuolar protein Tag1 and Atg1-Atg13 regulate autophagy termination during persistent starvation in S. cerevisiae.

Under starvation conditions, cells degrade their own components via autophagy in order to provide sufficient nutrients to ensure their survival. However, even if starvation persists, the cell is not completely degraded through autophagy, implying the existence of some kind of termination mechanism. In the yeast Saccharomyces cerevisiae, autophagy is terminated after 10-12 h of nitrogen starvation. In this study, we found that termination is mediated by re-phosphorylation of Atg13 by the Atg1 protein kinase, which is also affected by PP2C phosphatases, and the eventual dispersion of the pre-autophagosomal structure, also known as the phagophore assembly site (PAS). In a genetic screen, we identified an uncharacterized vacuolar membrane protein, Tag1, as a factor responsible for the termination of autophagy. Re-phosphorylation of Atg13 and eventual PAS dispersal were defective in the Δtag1 mutant. The vacuolar luminal domain of Tag1 and autophagic progression are important for the behaviors of Tag1. Together, our findings reveal the mechanism and factors responsible for termination of autophagy in yeast.