Presenting Author UT Southwestern Medical Center Dallas, Texas, United States
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. 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.
