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

Martonio Ponte Viana; Roman M Levytskyy; Ruchika Anand; Andreas S Reichert; Oleh Khalimonchuk

doi:10.1016/j.isci.2021.102119

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

iScience. 2021 Jan 29;24(2):102119. doi: 10.1016/j.isci.2021.102119. eCollection 2021 Feb 19.

Authors

Martonio Ponte Viana¹, Roman M Levytskyy¹, Ruchika Anand², Andreas S Reichert², Oleh Khalimonchuk^{1

3

4

5}

Affiliations

¹ Department of Biochemistry, University of Nebraska, Lincoln, NE 68588, USA.
² Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University of Dusseldorf, Dusseldorf 40225, Germany.
³ Nebraska Redox Biology Center, University of Nebraska, Lincoln, NE 68588, USA.
⁴ Center for Integrated Biomolecular Communication, University of Nebraska, Lincoln, NE 68588, USA.
⁵ Fred & Pamela Buffett Cancer Center, Omaha, NE 68198, USA.

Abstract

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.

Keywords: Cell Biology; Molecular Biology; Organizational Aspects of Cell Biology.

Abstract

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