ABSTRACT
Mitochondria surrounding lipid droplets (Peri-Droplet Mitochondria;PDM) maintain a unique proteome which is not equilibrated with the rest of the mitochondrial population. We find that PDM remain stationary and elongated on lipid droplets, fuel lipid droplet expansion, and do not fuse with cytosolic mitochondria. Compared to cytosolic mitochondria, PDM have higher capacity to metabolize pyruvate but reduced capacity to oxidize fatty acids. We reveal for the first time the mechanism by which the elongated mitochondrial shape of PDM differentiate their fuel preference from that of cytosolic mitochondria. We find that mitochondrial elongation reduces fatty acid utilization by inhibiting CPT1 activity. On the other hand, we find that mitochondrial fragmentation, such as observed in NASH, increases mitochondrial lipid utilization and may act as a compensatory mechanism to reduce lipotoxicity. Indeed, inhibition of fission in a model of NASH exacerbated NASH phenotype. We developed a cell-based imaging for the quantification of mitochondria-lipid droplet association and identified a set of small molecules that detach mitochondria from lipid droplets (PDM-Detachers). New unpublished data demonstrate PDM detachers induce lipolysis and lipid droplet shrinkage. Using these tools we assessed the role of lipid droplets in SARS-CoV2 expansion. We find that proliferation of various coronaviruses can be strongly inhibited by PDM-detachers and enhanced by attaching mitochondria to lipid droplets. We demonstrate that PDM can be found in humans. We studied adipose tissue from pheochromocytoma patients, a model of white adipose browning characterized by enhanced capacity for energy expenditure. Remarkably, bioenergetic changes associated with browning were primarily localized to PDM. Similar changes were found in a mouse model of re-browning, where PDM increased in whitened brown adipose tissue upon reducing housing temperature. Copyright © 2022
ABSTRACT
Objective: To compare the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine used for the vaccination in public security officers with different immunization schedules. Methods: From January to February, 2021, 405 public security officers in Taiyuan were randomly divided into 3 groups. Two doses of SARS-CoV-2 inactivated vaccine were injected according to the immunization schedule of 0-14 days, 0-21 days or 0-28 days, respectively. The nucleic acid of SARS-CoV-2 was detected by reverse transcription polymerase chain reaction. The neutralizing antibodies to SARS-CoV-2 were tested by microdose cytopathogenic efficiency assay of live virus. The GMT, seroconversion rate of SARS-CoV-2 neutralizing antibody and safety of the vaccine were analyzed for the 3 groups. Results: The seroconversion rate of SARS-CoV-2 neutralizing antibody was 100% in all the 3 groups. The SARS-CoV-2 neutralizing antibody level of 0-21 day group [166.70 (95%CI: 148.30-185.10)] was similar to that of 0-28 day group [179.50 (95%CI: 156.50-202.60)] (P>0.05), significantly higher than that of 0-14 day group [86.08 (95%CI: 72.36-99.80)] (P<0.001). The incidence rates of adverse reaction in the 3 groups were 1.48% (2/135), 0.74% (1/136) and 1.49% (2/134) respectively (P=0.750), all the adverse reactions were mild. Conclusions: The vaccination of inactivated SARS-CoV-2 vaccine with different immunization schedules in public security officers showed good safety and high seroconversion rate, and the GMTs of SARS-CoV-2 neutralizing antibody in 0-21 day group and 0-28 day group were higher than that in 0-14 day group.