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Updated: Mar 10, 2026

Author Spotlight: Unveiling Mitochondrial Contact Sites and Architectural Insights
Published on: June 16, 2023
Optic Atrophy 1 Is Epistatic to the Core MICOS Component MIC60 in Mitochondrial Cristae Shape Control
Christina Glytsou1, Enrique Calvo2, Sara Cogliati3
1Department of Biology, University of Padova, Padova 35121, Italy; IRCCS Fondazione Santa Lucia, Rome 00179, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Padova 35129, Italy.
Abstract:
The mitochondrial contact site and cristae organizing system (MICOS) and Optic atrophy 1 (OPA1) control cristae shape, thus affecting mitochondrial function and apoptosis. Whether and how they physically and functionally interact is unclear. Here, we provide evidence that OPA1 is epistatic to MICOS in the regulation of cristae shape. Proteomic analysis identifies multiple MICOS components in native OPA1-containing high molecular weight complexes disrupted during cristae remodeling. MIC60, a core MICOS protein, physically interacts with OPA1, and together, they control cristae junction number and stability, OPA1 being epistatic to MIC60. OPA1 defines cristae width and junction diameter independently of MIC60. Our combination of proteomics, biochemistry, genetics, and electron tomography provides a unifying model for mammalian cristae biogenesis by OPA1 and MICOS.
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