Mitochondrial Complexes I and II Are More Susceptible to Autophagy Deficiency in Mouse beta-Cells

BACKGROUND: Damaged mitochondria are removed by autophagy. Therefore, impairment of autophagy induces the accumulation of damaged mitochondria and mitochondrial dysfunction in most mammalian cells. Here, we investigated mitochondrial function and the expression of mitochondrial complexes in autophagy-related 7 (Atg7)-deficient beta-cells. METHODS: To evaluate the effect of autophagy deficiency on mitochondrial function in pancreatic beta-cells, we isolated islets from Atg7(F/F):RIP-Cre+ mice and wild-type littermates. Oxygen consumption rate and intracellular adenosine 5'-triphosphate (ATP) content were measured. The expression of mitochondrial complex genes in Atg7-deficient islets and in beta-TC6 cells transfected with siAtg7 was measured by quantitative real-time polymerase chain reaction. RESULTS: Baseline oxygen consumption rate of Atg7-deficient islets was significantly lower than that of control islets (P<0.05). Intracellular ATP content of Atg7-deficient islets during glucose stimulation was also significantly lower than that of control islets (P<0.05). By Oxygraph-2k analysis, mitochondrial respiration in Atg7-deficient islets was significantly decreased overall, although state 3 respiration and responses to antimycin A were unaffected. The mRNA levels of mitochondrial complexes I, II, III, and V in Atg7-deficient islets were significantly lower than in control islets (P<0.05). Down-regulation of Atg7 in beta-TC6 cells also reduced the expression of complexes I and II, with marginal significance (P<0.1). CONCLUSION: Impairment of autophagy in pancreatic beta-cells suppressed the expression of some mitochondrial respiratory complexes, and may contribute to mitochondrial dysfunction. Among the complexes, I and II seem to be most vulnerable to autophagy deficiency.

Type B Acute Aortic Dissection: The Prognosis and Fate of the Dissected Lumen of Nonsurgical Treated Patients / 日本心臓血管外科学会雑誌

From March 1981 to March 1990, 61 patients with Stanford type B acute aortic dissection were initially treated by conservative therapy. Among these 61 patients, the dissected lumen became occluded due to thrombosis early after diagnosis in 25 patients (Group T) and remained patent in 36 patients (Group P). Twentythree patients in Group T (92%) and 22 patients in Group P (61%) were discharged without major complications related to acute aortic dissection. However, 2 patients in Group T (8%) and 14 patients in Group P (39%) required additional surgical therapy or died during hospitalization. The mean aortic diameter at the time of admission in Group T was smaller than that of Group P (38±3mm vs 43±7mm, <i>p</i><0.05). During the observation period, there was a tendency for the diameter of the dissected aorta in Group T to decrease, but to increase in Group P. Long-term survival appeared to be better in Group T than in Group P, but there was no significant difference in the overall survival curve. Large aortic diameter at the time of admission and the presence of a true thoracic aortic aneurysm were major contributing factors influencing the prognosis. A long-term follow-up study showed that the dissected lumen reduced or disappeared in 14 of 23 patients in Group T (61%) but only 2 of 16 patients in Group P (12.5%). We concluded that the patients with small dissected aortas and thrombosed dissected lumens (Group T) can recuperate only with conservative therapy. However, patients with large dissected aortas and patent dissected lumen (Group P) may require surgical therapy even in Stanford type B aortic dissection.