Mitochondria, the cellular powerhouses, are dynamic organelles with central roles in cellular energetics, metabolism and signalling. We have identified the mitochondrial contact site and cristae organizing system (MICOS), a large membrane protein complex of more than 2 MDa located in the mitochondrial inner membrane. MICOS forms multiple contact sites with proteins of the mitochondrial outer membrane, intermembrane space and matrix and thus likely represents a large platform that connects machineries of different function, ranging from protein translocation to metabolite transport, membrane dynamics, respiration, mitochondrial genome transmission and endoplasmic reticulum-mitochondria contact sites. We aim to understand the dynamic organization of MICOS in a membrane-spanning network. Which signalling pathways and metabolic conditions alter the biogenesis, dynamics and turnover of the MICOS network and its regulatory functions on protein biogenesis, membrane dynamics, bioenergetics and inheritance?

Keywords

mitochondria, membrane network, metabolism, signalling, protein biogenesis

10 selected publications:

• Dual role of Mic10 in mitochondrial cristae organization and ATP synthase-linked metabolic adaptation and respiratory growth.
  Rampelt H, Wollweber F, Licheva M, de Boer R, Perschil I, Steidle L, Becker T, Bohnert M, van der Klei I, Kraft C, van der Laan M, Pfanner N (2022)
  Cell Rep. 38, 110290.
• Mitochondrial proteins: from biogenesis to functional networks.
  Pfanner N, Warscheid B, Wiedemann, N (2019)
  Nat Rev Mol Cell Biol 20, 267-284.
• Structure of the mitochondrial import gate reveals distinct preprotein paths.
  Araiso Y, Tsutsumi A, Qiu J, Imai K, Shiota T, Song J, Lindau C, Wenz LS, Sakaue H, Yunoki K, Kawano S, Suzuki J, Wischnewski M, Schütze C, Ariyama H, Ando T, Becker T, Lithgow T, Wiedemann N, Pfanner N, Kikkawa M, Endo T (2019)
  Nature 575, 395-401.
• Dual role of mitochondrial porin in metabolite transport across the outer membrane and protein transfer to the inner membrane.
  Ellenrieder L, Dieterle MP, Doan KN, Martensson CU, Floerchinger A, Campo ML, Pfanner N*,#, Becker, T* (2019)
  *corresponding #lead contact
• Membrane protein insertion through a mitochondrial β-barrel gate.
  Höhr AIC, Lindau C, Wirth C, Qiu J, Stroud DA, Kutik S, Guiard B, Hunte C, Becker T, Pfanner N*, Wiedemann N* (2018).
  Science 359, eaah6834   *corresponding
• Mitochondrial OXA translocase plays a major role in biogenesis of inner-membrane proteins.
  Stiller SB, Höpker J, Oeljeklaus S, Schütze C, Schrempp SG, Vent-Schmidt J, Horvath SE, Frazier AE, Gebert N, van der Laan M, Bohnert M, Warscheid B, Pfanner N*, Wiedemann, N* (2016).
  Cell Metab. 23, 901-8.
  *corresponding
• Central role of Mic10 in the mitochondrial contact site and cristae organizing system.
  Bohnert M, Zerbes RM, Davies KM, Mühleip AW, Rampelt H, Horvath SE, Boenke T, Kram A, Perschil I, Veenhuis M, Kühlbrandt W, van der Klei IJ, Pfanner N*, van der Laan M* (2015).
  Cell Metab. 21, 747-55.
  *corresponding
• Cell cycle-dependent regulation of mitochondrial preprotein translocase.
  Harbauer AB, Opalińska M, Gerbeth C, Herman JS, Rao S, Schönfisch B, Guiard B, Schmidt O, Pfanner N*, Meisinger C* (2014).
  Science 346, 1109-13.
  *corresponding
• Mgr2 functions as lateral gatekeeper for preprotein sorting in the mitochondrial inner membrane.
  Ieva R, Schrempp SG, Opaliński L, Wollweber F, Höß P, Heißwolf AK, Gebert M, Zhang Y, Guiard B, Rospert S, Becker T, Chacinska A, Pfanner N*, van der Laan M* (2014).
  Mol Cell 56, 641-52.
  *corresponding
• Regulation of mitochondrial protein import by cytosolic kinases.
  Schmidt O, Harbauer AB, Rao S, Eyrich B, Zahedi RP, Stojanovski D, Schönfisch B, Guiard B, Sickmann A, Pfanner N*, Meisinger C* (2011).
  Cell 144, 227-39.
  *corresponding