Protease OMA1 modulates mitochondrial bioenergetics and ultrastructure through dynamic association with MICOS complex

• Published in: iScience 2021-02, Vol.24 (2), p.102119, Article 102119
• Main Authors: Viana, Martonio Ponte, Levytskyy, Roman M., Anand, Ruchika, Reichert, Andreas S., Khalimonchuk, Oleh
• Format: Article
• Language: English
• Subjects: Cell Biology; Molecular Biology; Organizational Aspects of Cell Biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2021.102119

Remodeling of mitochondrial ultrastructure is a process that is critical for organelle physiology and apoptosis. Although the key players in this process—mitochondrial contact site and cristae junction organizing system (MICOS) and Optic Atrophy 1 (OPA1)—have been characterized, the mechanisms behind its regulation remain incompletely defined. Here, we found that in addition to its role in mitochondrial division, metallopeptidase OMA1 is required for the maintenance of intermembrane connectivity through dynamic association with MICOS. This association is independent of OPA1, mediated via the MICOS subunit MIC60, and is important for stability of MICOS and the intermembrane contacts. The OMA1-MICOS relay is required for optimal bioenergetic output and apoptosis. Loss of OMA1 affects these activities; remarkably it can be alleviated by MICOS-emulating intermembrane bridge. Thus, OMA1-dependent ultrastructure support is required for mitochondrial architecture and bioenergetics under basal and stress conditions, suggesting a previously unrecognized role for OMA1 in mitochondrial physiology. [Display omitted] •Metalloprotease OMA1 is physically associated with MICOS complex•OMA1-MICOS association is important for intermembrane connectivity•Membrane bridging alleviates bioenergetic and apoptotic defects in oma1−/− cells•Previously unrecognized role of OMA1 in mitochondrial physiology is revealed Molecular Biology; Cell Biology; Organizational Aspects of Cell Biology