A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria

Abstract

Statement MITO-MAP, a high-density genetic interaction map in budding yeast, identifies a mitochondrial inner membrane–associated complex that promotes normal mitochondrial membrane organization and morphology.

The presequence pathway is involved in protein sorting to the mitochondrial outer membrane

“…Om45 forms a complex with the outer membrane proteins porin and Om14. It has been reported that Om45 is involved in the interaction between outer and inner membrane protein complexes [18,19], thus linking the porin pore to transport proteins of the inner membrane. Studies conducted so far did not lead to the identification of proteinaceous factors required for the import of the Om45 precursor into mitochondria [7,8,13,17].…”

Mic60/Mitofilin determines MICOS assembly essential for mitochondrial dynamics and mtDNA nucleoid organization

“…Recently, several groups identified a large protein complex, MICOS complex (mitochondrial contact site and cristae organizing system; previously named MINOS, MitOS, Mitofilin or Fcj1 complex ), that has a crucial role in the formation of cristae junctions, contact sites to the outer membrane, and the organization of inner membrane. [10][11][12][13][14] In yeast, MICOS consists of at least six subunits: Mic60 (Fcj1), Mic10 (Mio10/Mcs10/Mos1), Mic19 (Aim13/Mcs19), Mic26 (Mio27/Mcs29/Mos2), Mic12 (Aim5/ Msc12) and Mic27 (Aim37/Mcs27). In mammals, five subunits of MICOS have already been identified, including Mic60 (Mitofilin/IMMT), Mic10 (MINOS1), Mic19 (CHCHD3/MINOS3), Mic25 (CHCHD6/CHCM1) and Mic27 (APOOL).…”

Mitofilin complexes: conserved organizers of mitochondrial membrane architecture

“…In human cells, mitofilin was found to interact with the sorting and assembly machinery of the outer membrane (SAM complex) that has a central role in the biogenesis of outer membrane proteins ( Figure 2B) (Xie et al , 2007 ;Darshi et al , 2011 ;Alkhaja et al , 2012 ;Ott et al , 2012 ). In yeast, interactions of mitofilincontaining protein complexes of the inner membrane with the SAM complex, the TOM complex, porin channels and Ugo1 have been reported (Figure 2A) (Harner et al , 2011 ;Hoppins et al , 2011 ;von der Malsburg et al , 2011 ;K ö rner et al, 2012 ;Zerbes et al , 2012 ). The interaction of mitofilin with the TOM complex was shown to support the import of precursor proteins into the intermembrane space via the mitochondrial intermembrane space assembly (MIA) machinery (von der Malsburg et al , 2011 ).…”

“…Several recent studies have reported on the discovery of a multi-subunit protein complex of the mitochondrial inner membrane in S. cerevisiae that contains mitofilin as a central component (Harner et al , 2011 ;Hoppins et al , 2011 ;von der Malsburg et al , 2011 ;Alkhaja et al , 2012 ). This protein complex was named the mitochondrial inner membrane organizing system (MINOS) or, alternatively, mitochondrial organizing structure (MitOS) or mitochondrial contact site (MICOS) complex (for an overview of the nomenclature see Herrmann , 2011 ).…”

“…The Saccharomyces cerevisiae mitofilin protein (also termed formation of crista junctions 1/Fcj1) was the first protein shown to be mainly located at crista junctions Harner et al , 2011 ). Depletion of mitofilin in human cells and worms or deletion of mitofilin in yeast leads to an extension of the inner membrane surface, a massive loss of crista junctions and to abnormal crista structures that appear as stacked lamellae disconnected from the inner boundary membrane (John et al , 2005 ;Rabl et al , 2009 ;Mun et al , 2010 ;Harner et al , 2011 ;Hoppins et al , 2011 ;von der Malsburg et al , 2011 ;Alkhaja et al , 2012 ). These observations point to a conserved function of mitofilin in the formation and/or maintenance of crista junctions.…”