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bioRxiv · 10.1101/2022.03.29.486240

The outer mitochondrial membrane protein TMEM11 is a novel negative regulator of BNIP3/BNIP3L-dependent receptor-mediated mitophagy

Gok, M. O.·Friedman, J. R.
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Abstract

Mitochondria play critical roles in cellular metabolism and to maintain their integrity, they are regulated by several quality control pathways, including mitophagy. During BNIP3/BNIP3L-dependent receptor-mediated mitophagy, mitochondria are selectively degraded by the direct recruitment of the autophagosome biogenesis protein LC3. BNIP3 and/or BNIP3L are upregulated situationally, for example during hypoxia and developmentally during erythrocyte maturation. However, it is not well understood how they are regulated at steady-state. Here, we find that the poorly characterized mitochondrial cristae morphology regulator TMEM11 unexpectedly localizes to the outer membrane where it forms a complex with BNIP3 and BNIP3L. Loss of TMEM11 causes mitochondrial morphology defects in a BNIP3/BNIP3L-dependent manner and, further, we find that mitophagy is hyper-active in the absence of TMEM11 during both normoxia and hypoxia. Our results reveal a non-canonical role for TMEM11 as a negative regulator of BNIP3/BNIP3L-mediated mitophagy and suggest that the TMEM11/BNIP3/BNIP3L complex coordinately regulates mitochondrial quality control.

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Gok, M. O., Friedman, J. R.. 2022-03-29. The outer mitochondrial membrane protein TMEM11 is a novel negative regulator of BNIP3/BNIP3L-dependent receptor-mediated mitophagy. https://doi.org/10.1101/2022.03.29.486240

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