Protein Biogenesis and Architecture of Mitochondria
Nikolaus Pfanner Institute of Biochemistry and Molecular Biology, University of Freiburg, Freiburg, Germany
Mitochondria are essential cell organelles with multiple functions in bioenergetics, metabolism and signaling. Mitochondria consist of two membranes and two aqueous compartments and contain about 1,000 different proteins. Most proteins are synthesized as precursor proteins on cytosolic ribosomes. Targeting signals of the precursor proteins are recognized by receptors on the mitochondrial surface, followed by translocation across the mitochondrial membranes. Four major pathways of protein import into mitochondria use the general translocase of the outer membrane (TOM). The precursor proteins are subsequently sorted via different machineries: the presequence translocase of the inner membrane (TIM23), the carrier translocase of the inner membrane (TIM22), the mitochondrial intermembrane space import and assembly (MIA) machinery, or the sorting and assembly machinery (SAM) of the outer membrane. A fifth protein import pathway can bypass the TOM channel and uses the mitochondrial import (MIM) complex for insertion of precursor proteins into the outer membrane. The mitochondrial contact site and cristae organizing system (MICOS) is a large multi-subunit protein complex of the inner membrane that is preferentially located at crista junctions. MICOS forms contact sites with TOM, SAM and further proteins of the outer membrane and is the core of a large network that controls mitochondrial architecture and biogenesis.
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