A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria

TLDR

The authors constructed a quantitative, high‑density genetic interaction map (MITO‑MAP) in yeast to explore mitochondrial structure, function, and communication with other pathways, and propose that the identified MitOS complex serves as a conserved mitochondrial skeletal structure that delineates inner‑membrane regions to establish normal architecture. They generated the MITO‑MAP by measuring genetic interactions across the yeast genome, producing a high‑density quantitative map of mitochondrial function. The MITO‑MAP uncovered a previously uncharacterized inner‑membrane complex, MitOS, composed of Fcj1/Mitofilin and five additional proteins, which physically associates with both inner and outer membrane components, interacts with ATP synthase dimers, and is essential for organizing the inner membrane and maintaining normal mitochondrial morphology, while also revealing broader.

Abstract

To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane–associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria.