Dual Role of Mitochondrial Porin in Metabolite Transport across the Outer Membrane and Protein Transfer to the Inner Membrane

• Published in: Molecular cell Vol. 73; no. 5; pp. 1056 - 1065.e7
• Main Authors: Ellenrieder, Lars, Dieterle, Martin P., Doan, Kim Nguyen, Mårtensson, Christoph U., Floerchinger, Alessia, Campo, María Luisa, Pfanner, Nikolaus, Becker, Thomas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.03.2019
• Subjects: membrane contact sites; metabolite carrier; mitochondria; protein sorting; protein translocation; metabolite carrier; protein sorting; membrane contact sites; mitochondria; protein translocation
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2018.12.014

The mitochondrial inner membrane harbors a large number of metabolite carriers. The precursors of carrier proteins are synthesized in the cytosol and imported into mitochondria by the translocase of the outer membrane (TOM) and the carrier translocase of the inner membrane (TIM22). Molecular chaperones in the cytosol and intermembrane space bind to the hydrophobic precursors to prevent their aggregation. We report that the major metabolite channel of the outer membrane, termed porin or voltage-dependent anion channel (VDAC), promotes efficient import of carrier precursors. Porin interacts with carrier precursors arriving in the intermembrane space and recruits TIM22 complexes, thus ensuring an efficient transfer of the precursors to the inner membrane translocase. Porin channel mutants impaired in metabolite transport are not disturbed in carrier import into mitochondria. We conclude that porin serves distinct functions as outer membrane channel for metabolites and as coupling factor for protein translocation into the inner membrane. [Display omitted] •Metabolite channel of mitochondrial outer membrane promotes protein import•Porin interacts with carrier precursors accumulated in the intermembrane space•Porin recruits the carrier translocase of the inner mitochondrial membrane•Dual role of porin as metabolite channel and as coupling factor in protein import Ellenrieder et al. report that the major metabolite channel porin of the mitochondrial outer membrane promotes the import of carrier proteins to the mitochondrial inner membrane. Porin binds carrier precursors in the intermembrane space and recruits the carrier translocase of the inner membrane to facilitate transfer of the precursor proteins.