OPA1 functionally interacts with MIC60 but is dispensable for crista junction formation

Abstract

Edited by Miguel De la RosaRemodeling of crista junctions (CJs) is observed in numerous human disorders and during apoptosis. The functional interplay of OPA1 and MIC60, two key players in this context, is unclear. We show that OPA1 modulates cristae morphology but is dispensable for CJ formation. MIC60 is strongly enriched at CJs, whereas OPA1 is distributed evenly across the inner membrane. MIC60 levels are increased in OPA1À/À cells which show increased cellular resistance to apoptosis induction. Endogenous OPA1 and MIC60 show a physical interaction. Overall, we suggest that the regulation of CJ remodeling during apoptosis is mediated via an interplay between OPA1 and MIC60.

Optic Atrophy 1 Is Epistatic to the Core MICOS Component MIC60 in Mitochondrial Cristae Shape Control

“…This comprehensive morphometry analysis revealed that (1) OPA1 is the sole regulator of CLW and CJW, (2) OPA1 and MIC60 lie in the same pathway controlling CJ number and stability, and (2) surprisingly, OPA1 is epistatic to MIC60. While this work was under revision, Barrera et al., (2016) confirmed that OPA1 and MIC60 interact physically and that levels of the former affect CJ number. However, whether they lie in the same genetic pathway and how they are relatively positioned in the control of the multiple parameters of cristae shape was not addressed (Barrera et al., 2016).…”

“…While this work was under revision, Barrera et al., (2016) confirmed that OPA1 and MIC60 interact physically and that levels of the former affect CJ number. However, whether they lie in the same genetic pathway and how they are relatively positioned in the control of the multiple parameters of cristae shape was not addressed (Barrera et al., 2016). …”

Regulated membrane remodeling by Mic60 controls formation of mitochondrial crista junctions

“…Also the mitochondrial dynamin-like OPA1 GTPase has been shown to play a crucial role in cristae remodelling and mitochondrial fusion1718205152. Furthermore, a direct involvement of the MICOS component Mic10 in creating membrane curvature was recently demonstrated3338 indicating that Mic10 directly participates in mitochondrial membrane remodelling by oligomerization.…”

“…Cristae are linked to the IBM via tubular openings of defined diameter termed crista junctions (CJs)710. It has been proposed that cristae formation and dynamics may be connected to the mitochondrial fusion and fission machineries171819. Perturbations of these processes are observed in numerous pathologies including neurodegenerative diseases and cancer124.…”

“…The mammalian MICOS complex contains at least one additional subunit (Mic25) and a number of MICOS-interacting proteins have been reported (summarized in refs 26, 27). Recent studies indicate that CJ formation and maintenance in mammals is controlled by an intricate interplay between MICOS and the dynamin-like GTPase OPA1 (refs 17, 18). …”