Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion.

ABSTRACT: OPA1, a large GTPase of the dynamin superfamily, mediates fusion of the mitochondrial inner membranes, regulates cristae morphology, and maintains respiratory chain function. Inner membrane-anchored long forms of OPA1 (l-OPA1) are proteolytically processed by the OMA1 or YME1L proteases, acting at cleavage sites S1 and S2, respectively, to produce short forms (s-OPA1). In both mice and humans, half of the mRNA splice forms of Opa1 are constitutively processed to yield exclusively s-OPA1. However, the function of s-OPA1 in mitochondrial fusion has been debated, because in some stress conditions, s-OPA1 is dispensable for fusion. By constructing cells in which the Opa1 locus no longer produces transcripts with S2 cleavage sites, we generated a simplified system to identify the

SUBMITTER: Wang R 

PROVIDER: S-EPMC8120690 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature