Abstract
The mitochondrial outer membrane is essential for communication between mitochondria and the rest of the cell and facilitates the transport of metabolites, ions, and proteins. All mitochondrial outer membrane channels known to date are β-barrel membrane proteins, including the abundant voltage-dependent anion channel and the cation-preferring protein-conducting channels Tom40, Sam50, and Mdm10. We analyzed outer membrane fractions of yeast mitochondria and identified four new channel activities: two anion-preferring channels and two cation-preferring channels. We characterized the cation-preferring channels at the molecular level. The mitochondrial import component Mim1 forms a channel that is predicted to have an α-helical structure for protein import. The short-chain dehydrogenase-related protein Ayr1 forms an NADPH-regulated channel. We conclude that the mitochondrial outer membrane contains a considerably larger variety of channel-forming proteins than assumed thus far. These findings challenge the traditional view of the outer membrane as an unspecific molecular sieve and indicate a higher degree of selectivity and regulation of metabolite fluxes at the mitochondrial boundary.
Highlights
Mitochondria fulfill essential functions in cellular energetics, metabolism, and physiology (Neupert and Herrmann, 2007; Youle and van der Bliek, 2012; Labbé et al, 2014; Lill et al, 2014; Wai and Langer, 2016; Braun and Westermann, 2017; Wiedemann and Pfanner, 2017)
This study reveals an unexpected diversity of mitochondrial outer membrane channels (OMCs)
A systematic analysis of the yeast genome indicated that yeast contains no more than five membrane-integral β-barrel proteins (Imai et al, 2008; Kutik et al, 2008b; Zeth, 2010), the fifth one being the minor voltage-dependent anion channel (VDAC) isoform Por2 that does not affect outer membrane permeability (Lee et al, 1998)
Summary
Mitochondria fulfill essential functions in cellular energetics, metabolism, and physiology (Neupert and Herrmann, 2007; Youle and van der Bliek, 2012; Labbé et al, 2014; Lill et al, 2014; Wai and Langer, 2016; Braun and Westermann, 2017; Wiedemann and Pfanner, 2017). The outer membrane forms the barrier of mitochondria to the cytosol and is responsible for the transport of a large number of metabolites, ions, and precursor proteins (Neupert and Herrmann, 2007; Endo and Yamano, 2010; Hiller et al, 2010; Peixoto et al, 2010; Schmidt et al, 2010; Harsman et al, 2011; Hewitt et al, 2011; Colombini, 2012). The other known outer membrane channels (OMCs) transport precursor proteins including the main protein import channel Tom of the translocase of outer mitochondrial membrane complex, the channel Sam of the sorting and assembly machinery, and the mitochondrial distribution and morphology protein Mdm.
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