The mitochondrial inner membrane consists of two domains, inner boundary membrane and cristae membrane that are connected by crista junctions. Mitofilin/Fcj1 was reported to be involved in formation of crista junctions, however, different views exist on its function and possible partner proteins. We report that mitofilin plays a dual role. Mitofilin is part of a large inner membrane complex, and we identify five partner proteins as constituents of the mitochondrial inner membrane organizing system (MINOS) that is required for keeping cristae membranes connected to the inner boundary membrane. Additionally, mitofilin is coupled to the outer membrane and promotes protein import via the mitochondrial intermembrane space assembly pathway. Our findings indicate that mitofilin is a central component of MINOS and functions as a multifunctional regulator of mitochondrial architecture and protein biogenesis.

No abstract

Proteins are macromolecules, which perform a large variety of functions. Most of them have only a single function, but an increasing number of proteins are being identified as multifunctional. Moonlighting proteins form a special class of multifunctional proteins. They perform multiple autonomous and often unrelated functions without partitioning these functions into different domains of the protein. Striking examples are enzymes, which in addition to their catalytic function are involved in fully unrelated processes such as autophagy, protein transport or DNA maintenance. In this contribution we present an overview of our current knowledge of moonlighting proteins and discuss the significant implications for biomedical and fundamental research.