| First Author | Wang R | Year | 2021 |
| Journal | Mol Biol Cell | Volume | 32 |
| Issue | 2 | Pages | 157-168 |
| PubMed ID | 33237841 | Mgi Jnum | J:309720 |
| Mgi Id | MGI:6759609 | Doi | 10.1091/mbc.E20-09-0605 |
| Citation | Wang R, et al. (2021) Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion. Mol Biol Cell 32(2):157-168 |
| abstractText | 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 new YME1L-dependent site S3 that mediates constitutive and complete cleavage of OPA1. We show that mitochondrial morphology is highly sensitive to the ratio of l-OPA1 to s-OPA1, indicating that s-OPA1 regulates mitochondrial fusion. |
