Serum starvation induces anti-apoptotic cIAP1 to promote mitophagy through ubiquitination

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 regulate...

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Published in:Biochemical and biophysical research communications 2016-10, Vol.479 (4), p.940-946
Main Authors: Mukhopadhyay, Subhadip, Naik, Prajna Paramita, Panda, Prashanta Kumar, Sinha, Niharika, Das, Durgesh Nandini, Bhutia, Sujit Kumar
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Apoptosis
Apoptosis - physiology
Biological Transport, Active
cIAP1
Culture Media, Serum-Free
HeLa Cells
Humans
Inhibitor of Apoptosis Proteins - metabolism
Membrane Transport Proteins - metabolism
Microtubule-Associated Proteins - metabolism
Mitochondria
Mitochondrial Degradation - physiology
Mitochondrial Dynamics - physiology
Mitophagy
Oxygen Consumption
Receptors, Cell Surface - metabolism
Serum starvation
Stress, Physiological
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
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Summary: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. [Display omitted]
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2016.09.143