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

Abstract

Highlights d Metabolite channel of mitochondrial outer membrane promotes protein import d Porin interacts with carrier precursors accumulated in the intermembrane space d Porin recruits the carrier translocase of the inner mitochondrial membrane d Dual role of porin as metabolite channel and as coupling factor in protein import

The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments

“…1d) like the mature assembled MPC dimers detected by Western blotting (Additional file 1: Figure S1a-d) [1,6]. The relatively slow migration of the~30 kDa MPC dimers on blue native electrophoresis is likely due to considerable amounts of lipids and detergent bound to MPC, similar to observations with other small membrane proteins [7,26,34,35]. In the absence of a membrane potential Δψ, the transport to a protease-protected location was impaired and the assembly into the~150 kDa complex was blocked ( Fig.…”

“…Precursor proteins imported via the presequence pathway are typically recognized by the receptor Tom20, whereas canonical carrier precursors are recognized by Tom70 [17,35,[37][38][39][40][41][42]. Import and assembly of Mpc2 and Mpc3 into tom20Δ mitochondria were not inhibited, but even slightly better than that into wild-type mitochondria, whereas import of the presequence pathway substrate F 1 -ATPase subunit β (F 1 β) was inhibited in the mutant mitochondria as expected ( Fig.…”

Depletion of voltage-dependent anion channel (VDAC) ofToxoplasma gondiiaffects multiple mitochondrial functions, but not calcium signalling

“…Beyond small molecules, VDAC also has a role in mitochondrial protein import in both plants and yeast through interacting with components of the translocon machinery (Ellenrieder et al, 2019;Salinas et al, 2006). To determine if depletion of VDAC affected mitochondrial protein import in T. gondii, we assessed the maturation of the mitochondrial-targeted marker HSP60L-DHFR-Myc (van Dooren et al, 2016) through its transient expression in iVDAC parasites (Fig.…”

“…In many eukaryotes, from protists to mammals, transport across the outer mitochondrial membrane is mediated by a conserved, highly abundant porin named the Voltage-Dependent Anion Channel (VDAC) (Hodge and Colombini, 1997;Homblé et al, 2012;Wideman et al, 2013). VDAC mediates the passage of ions, nucleotides and metabolites across the outer membrane, and has been implicated in protein and tRNA import in to the mitochondria (Camara et al, 2017;Ellenrieder et al, 2019;Hodge and Colombini, 1997;Salinas et al, 2006). Beyond mediating transfer across the outer membrane, VDAC has also been identified as component of membrane contact sites between the mitochondria and endoplasmic reticulum (ER).…”

The Yeast Voltage-Dependent Anion Channel Porin: More IMPORTant than Just Metabolite Transport

“…The abundant outer membrane channel Porin is a voltagedependent anion channel whose role in transporting metabolites and ions is well established but its role in protein import into mitochondria was hitherto unknown. Now, two papers by the Endo and Pfanner groups, respectively, elegantly describe a novel role for Porin whereby this protein plays a critical role in the transition of the TOM complex between the trimer and dimer states and directly impacts on the pathway that inserts the metabolite carrier proteins in the inner mitochondrial membrane ( Figure 1; Sakaue et al, 2019;Ellenrieder et al, 2019). Sakaue et al (2019) provide a comprehensive analysis of a novel role for yeast Porin in regulating the dynamic transition of the TOM complex from a trimeric to a dimeric state.…”