Abstract
Mitochondrial cristae are critical for efficient oxidative phosphorylation, however, how cristae architecture is precisely organized remains largely unknown. Here, we discovered that Mic19, a core component of MICOS (mitochondrial contact site and cristae organizing system) complex, can be cleaved at N-terminal by mitochondrial protease OMA1 under certain physiological stresses. Mic19 directly interacts with mitochondrial outer-membrane protein Sam50 (the key subunit of SAM complex) and inner-membrane protein Mic60 (the key component of MICOS complex) to form Sam50–Mic19–Mic60 axis, which dominantly connects SAM and MICOS complexes to assemble MIB (mitochondrial intermembrane space bridging) supercomplex for mediating mitochondrial outer- and inner-membrane contact. OMA1-mediated Mic19 cleavage causes Sam50–Mic19–Mic60 axis disruption, which separates SAM and MICOS and leads to MIB disassembly. Disrupted Sam50–Mic19–Mic60 axis, even in the presence of SAM and MICOS complexes, causes the abnormal mitochondrial morphology, loss of mitochondrial cristae junctions, abnormal cristae distribution and reduced ATP production. Importantly, Sam50 displays punctate distribution at mitochondrial outer membrane, and acts as an anchoring point to guide the formation of mitochondrial cristae junctions. Therefore, we propose that Sam50–Mic19–Mic60 axis-mediated SAM–MICOS complexes integration determines mitochondrial cristae architecture.
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Acknowledgements
This work is supported by National Natural Science Foundation of China (91854107 and 31671393), and the Fundamental Research Funds for the Central Universities (2042017kf0197 and 2042017kf0242).
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Tang, J., Zhang, K., Dong, J. et al. Sam50–Mic19–Mic60 axis determines mitochondrial cristae architecture by mediating mitochondrial outer and inner membrane contact. Cell Death Differ 27, 146–160 (2020). https://doi.org/10.1038/s41418-019-0345-2
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DOI: https://doi.org/10.1038/s41418-019-0345-2
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