Mitochondrial porin links protein biogenesis to metabolism
In this report, we summarize recent findings about a role of the outer membrane metabolite channel VDAC/porin in protein import into mitochondria. Mitochondria fulfill key functions for cellular energy metabolism. Their biogenesis involves the import of about 1000 different proteins that are produced as precursors on cytosolic ribosomes. The translocase of the outer membrane (TOM complex) forms the entry gate for mitochondrial precursor proteins. Dedicated protein translocases sort the preproteins into the different mitochondrial subcompartments. While protein transport pathways are analyzed to some detail, only little is known about regulatory mechanisms that fine-tune protein import upon metabolic signaling. Recently, a dual role of the voltage-dependent anion channel (VDAC), also termed porin, in mitochondrial protein biogenesis was reported. First, VDAC/porin promotes as a coupling factor import of carrier proteins into the inner membrane. Second, VDAC/porin regulates the formation of the TOM complex. Thus, the major metabolite channel in the outer membrane VDAC/porin connects protein import to mitochondrial metabolism.
KeywordsMitochondria TOM complex VDAC Protein import
The work was supported by grants of the Deutsche Forschungsgemeinschaft (BE 4679/2–2), Research Training Group 278002225/RTG 2202 and Germany’s Excellence Strategy (CIBSS-EXC-2189—Project ID 390939984). Work included in this study has also been performed in partial fulfillment of the requirements for the doctoral thesis of K.N.D. at the University of Freiburg.
- Ellenrieder L, Opaliński Ł, Becker L, Krüger V, Mirus O, Straub SP, Ebell K, Flinner N, Stiller SB, Guiard B, Meisinger C, Wiedemann N, Schleiff E, Wagner R, Pfanner N, Becker T (2016) Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10. Nat Commun 7:13021CrossRefGoogle Scholar
- Gebert N, Gebert M, Oeljeklaus S, von der Malsburg K, Stroud DA, Kulawiak B, Wirth C, Zahedi RP, Dolezal P, Wiese S, Simon O, Schulze-Specking A, Truscott KN, Sickmann A, Rehling P, Guiard B, Hunte C, Warscheid B, van der Laan M, Pfanner N, Wiedemann N (2011) Dual function of Sdh3 in the respiratory chain and TIM22 protein translocase of the mitochondrial inner membrane. Mol Cell 44:811–818CrossRefGoogle Scholar
- Kang Y, Stroud DA, Baker MJ, De Souza DP, Frazier AE, Liem M, Tull D, Mathivanan S, McConville MJ, Thorburn DR, Ryan MT, Stojanovski D (2017) Sengers syndrome-associated mitochondrial acylglycerol kinase is a subunit of the human TIM22 protein import complex. Mol Cell 67:457–475CrossRefGoogle Scholar
- Morgenstern M, Stiller SB, Lübbert P, Peikert CD, Dannenmaier S, Drepper F, Weill U, Höß P, Feuerstein R, Gebert M, Bohnert M, van der Laan M, Schuldiner M, Schütze C, Oeljeklaus S, Pfanner N, Wiedemann N, Warscheid B (2017) Definition of a high-confidence mitochondrial proteome at quantitative scale. Cell Rep 19:2836–2852CrossRefGoogle Scholar