Fang 2021 Cell Rep

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Fang H, Ye X, Xie J, Li Y, Li H, Bao X, Yang Y, Lin Z, Jia M, Han Q, Zhu J, Li X, Zhao Q, Yang Y, Lyu J (2021) A membrane arm of mitochondrial complex I sufficient to promote respirasome formation. Cell Rep 35:108963.

» PMID: 33852835 Open Access

Fang Hezhi, Ye Xianglai, Xie Jie, Li Yuanyuan, Li Haiyan, Bao Xinzhu, Yang Yue, Lin Zifan, Jia Manli, Han Qing, Zhu Jingjing, Li Xueyun, Zhao Qiongya, Yang Yanling, Lyu Jianxin (2021) Cell Rep

Abstract: The assembly pathways of mitochondrial respirasome (supercomplex I+III2+IV) are not fully understood. Here, we show that an early sub-complex I assembly, rather than holo-complex I, is sufficient to initiate mitochondrial respirasome assembly. We find that a distal part of the membrane arm of complex I (PD-a module) is a scaffold for the incorporation of complexes III and IV to form a respirasome subcomplex. Depletion of PD-a, rather than other complex I modules, decreases the steady-state levels of complexes III and IV. Both HEK293T cells lacking TIMMDC1 and patient-derived cells with disease-causing mutations in TIMMDC1 showed accumulation of this respirasome subcomplex. This suggests that TIMMDC1, previously known as a complex-I assembly factor, may function as a respirasome assembly factor. Collectively, we provide a detailed, cooperative assembly model in which most complex-I subunits are added to the respirasome subcomplex in the lateral stages of respirasome assembly. Keywords: Leigh syndrome, TIMMDC1, Cooperative assembly, Mitochondrial respirasome, Oxidative phosphorylation Bioblast editor: Plangger M


Labels: MiParea: Respiration 



Preparation: Permeabilized cells, Intact cells 


Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, S  HRR: Oxygraph-2k 

2021-04