CHCHD2 accumulates in distressed mitochondria and facilitates oligomerization of CHCHD10.

ABSTRACT: Mutations in paralogous mitochondrial proteins CHCHD2 and CHCHD10 cause autosomal dominant Parkinson Disease (PD) and Amyotrophic Lateral Sclerosis/Frontotemporal Dementia (ALS/FTD), respectively. Using newly generated CHCHD2, CHCHD10 and CHCHD2/10 double knockout cell lines, we find that the proteins are partially functionally redundant, similarly distributed throughout the mitochondrial cristae, and form heterodimers. Unexpectedly, we also find that CHCHD2/CHCHD10 heterodimerization increases in response to mitochondrial stress. This increase is driven by differences in the proteins' stability and mutual affinity: CHCHD2 is preferentially stabilized by loss of mitochondrial membrane potential, and CHCHD10 oligomerization depends on CHCHD2 expression. Exploiting the dependence of CHCHD10

SUBMITTER: Huang X 

PROVIDER: S-EPMC6216204 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature