Fang 2021 Cell Rep
|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.|
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