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Sci Rep. 2015 Nov 4;5:16064. doi: 10.1038/srep16064.

Mitofilin and CHCHD6 physically interact with Sam50 to sustain cristae structure.

Author information

1
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, and Medical Research Institute, Wuhan University, Wuhan, China.
2
Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
3
College of Life Sciences, Wuhan University, Wuhan, China.

Abstract

The inner mitochondrial membrane (IMM) invaginates to form cristae and the maintenance of cristae depends on the mitochondrial contact site (MICOS) complex. Mitofilin and CHCHD6, which physically interact, are two components of the MICOS. In this study, we performed immunoprecipitation experiments with Mitofilin and CHCHD6 antibodies and identified a complex containing Mitofilin, Sam50, and CHCHD 3 and 6. Using transcription activator-like effector nucleases (TALENs), we generated knockdown/knockout clones of Mitofilin and CHCHD6. Transmission electron microscopy (TEM) revealed that vesicle-like cristae morphology appeared in cell lines lacking Mitofilin, and mitochondria exhibited lower cristae density in CHCHD6-knockout cells. Immunoblot analysis showed that knockdown of Mitofilin, but not knockout of CHCHD6, affected their binding partners that control cristae morphology. We also demonstrated that Mitofilin and CHCHD6 directly interacted with Sam50. Additionally, we observed that Mitofilin-knockdown cells showed decreased mitochondrial membrane potential (ΔΨm) and intracellular ATP content, which were minimally affected in CHCHD6-knockout cells. Taken together, we conclude that the integrity of MICOS and its efficient interaction with Sam50 are indispensable for cristae organization, which is relevant to mitochondrial function.

PMID:
26530328
PMCID:
PMC4632003
DOI:
10.1038/srep16064
[Indexed for MEDLINE]
Free PMC Article

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