کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10814856 1058420 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pyruvate stimulates mitophagy via PINK1 stabilization
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Pyruvate stimulates mitophagy via PINK1 stabilization
چکیده انگلیسی
Damaged mitochondria are targeted for degradation by an autophagy pathway known as mitophagy. Despite efforts to unravel the mechanisms underlying mitophagy, aspects of mitophagy regulation remain largely unknown. In this study, by using a cell-based fluorescence assay reflecting CCCP-induced mitophagy, we have screened cDNA expression library encoding mitochondrial proteins and identified PDK4 as a mitophagy regulator. Ectopic expression of PDK4 stimulated the clearance of mitochondrial proteins during CCCP-induced mitophagy and enhanced pyruvate levels in both the cytosol and mitochondria. Interestingly, mitochondrial degradation during the mitophagy was not efficient in the absence of pyruvate. Pyruvate was required for PINK1 stabilization during mitochondrial depolarization and subsequent PARK2 translocation and LC3 recruitment onto damaged mitochondria. This pyruvate-mediated mitophagy was not affected by OXPHOS or cellular ATP levels, thus independent of energy metabolism. Rather, pyruvate was required for the interaction between PINK1 and TOMM20 under CCCP condition. These results suggest that pyruvate is required for CCCP-induced PINK1/PARK2-mediated mitophagy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 27, Issue 9, September 2015, Pages 1824-1830
نویسندگان
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