MINOS1 is a conserved component of mitofilin complexes and required for mitochondrial function and cristae organization

Abstract

MINOS1/Mio10, a conserved mitochondrial protein, is required for mitochondrial inner membrane organization and cristae morphology. MINOS1/Mio10 is a novel constituent of the mitofilin/Fcj1 complex of the inner membrane, linking the morphology phenotype of the mutant to the activity of the mitochondrial inner membrane organizing complex.

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

“…Deletion of MIO10 in yeast leads to reduced cell growth, the absence of assembled MINOS complexes and dramatic alterations of inner membrane architecture, including the formation of stacked, lamellar cristae and loss of crista junctions (Harner et al , 2011 ;Hoppins et al , 2011 ;von der Malsburg et al , 2011 ;Alkhaja et al , 2012 ). The morphological alterations observed in mitochondria of mio10 Δ cells are similar to those seen in mitofilin mutants, indicating that mitofilin and Mio10 are the core components of MINOS.…”

“…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 ).…”

“…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.…”