期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 479, 期 4, 页码 940-946出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.09.143
关键词
Serum starvation; Mitochondria; cIAP1; Mitophagy; Apoptosis; Ubiquitination
资金
- Department of Biotechnology [BT/PR7791/BRB/10/1187/2013]
- Science and Engineering Research Board (SERB), Department of Science and Technology [SR/SO/BB-0101/2012]
- Council of Scientific and Industrial Research (CSIR) Human Resource Development Group, Government of India [37(1608)/13/EMR-II]
Mitophagy is a highly specialised type of autophagy that plays an important role in regulating mitochondrial dynamics and controls cellular quality during stress. In this study, we established that serum starvation led to induction of cellular inhibitor of apoptosis protein-1 (cIAP1), which regulates mitophagy through ubiquitination. Importantly, gain and loss of function of cIAP1 resulted in concomitant alteration in mitophagy confirming the direct implication of cIAP1 in induction of mitophagy. Interestingly, it was observed that cIAP1 translocated to mitochondria to associate with TOM20, Ulk1, and LC3 to initiate mitophagy. Further, cIAP1-induced mitophagy led to dysfunctional mitochondria that resulted in abrogation of mitochondrial oxygen consumption rate along with the decrease in ATP levels. The ubiquitination of cIAP1 was found to be the critical regulator of mitophagy. The disruption of cIAP1-ubiquitin interaction by PYR41 ensured the abrogation of cIAP1-LC3 interaction and mitophagy inhibition. Our study revealed an important function of cIAP1 as a crucial molecular link between autophagy and apoptosis for regulation of mitochondrial dynamics to mitigate cellular stress. (C) 2016 Elsevier Inc. All rights reserved.
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