The short variant of the mitochondrial dynamin OPA1 maintains mitochondrial energetics and cristae structure.

Abstract

The protein optic atrophy 1 (OPA1) is a dynamin-related protein associated with the inner mitochondrial membrane and functions in mitochondrial inner membrane fusion and cristae maintenance. Inner membrane-anchored long OPA1 (L-OPA1) undergoes proteolytic cleavage resulting in short OPA1 (S-OPA1). It is often thought that S-OPA1 is a functionally insignificant proteolytic product of L-OPA1 because the accumulation of S-OPA1 due to L-OPA1 cleavage is observed in mitochondrial fragmentation and dysfunction. However, cells contain a mixture of both L- and S-OPA1 in normal conditions, suggesting the functional significance of maintaining both OPA1 forms, but the differential roles of L- and S-OPA1 in mitochondrial fusion and energetics are ill-defined. Here, we examined mitochondrial fusion and energetic activities in cells possessing L-OPA1 alone, S-OPA1 alone, or both L- and S-OPA1. Using a mitochondrial fusion assay, we established that L-OPA1 confers fusion competence, whereas S-OPA1 does not. Remarkably, we found that S-OPA1 alone without L-OPA1 can maintain oxidative phosphorylation function as judged by growth in oxidative phosphorylation-requiring media, respiration measurements, and levels of the respiratory complexes. Most strikingly, S-OPA1 alone maintained normal mitochondrial cristae structure, which has been commonly assumed to be the function of OPA1 oligomers containing both L- and S-OPA1. Furthermore, we found that the GTPase activity of OPA1 is critical for maintaining cristae tightness and thus energetic competency. Our results demonstrate that, contrary to conventional notion, S-OPA1 is fully competent for maintaining mitochondrial energetics and cristae structure.

• Authors: Hakjoo Lee, Sylvia B Smith, Yisang Yoon
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 292 Issue 17 Pg. 7115-7130 (04 28 2017) ISSN: 1083-351X [Electronic] United States
• PMID: 28298442 (Publication Type: Journal Article)
• Copyright: © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• DNA, Mitochondrial
• GTP Phosphohydrolases
• OPA1 protein, human
• Opa1 protein, mouse
• Oxygen

Topics

• Alternative Splicing
• Animals
• Apoptosis
• DNA, Mitochondrial (metabolism)
• Energy Metabolism
• Fibroblasts (metabolism)
• GTP Phosphohydrolases (chemistry, genetics)
• Genetic Variation
• Humans
• Mice
• Mice, Knockout
• Microscopy, Electron, Transmission
• Mitochondria (metabolism)
• Mitochondrial Dynamics
• Mitochondrial Membranes (metabolism)
• Oxidative Phosphorylation
• Oxygen (chemistry)
• Phosphorylation
• Proteolysis