The C-terminal domain of Fcj1 is required for formation of crista junctions and interacts with the TOB/SAM complex in mitochondria

Abstract

The molecular mechanisms determining mitochondrial architecture are largely unclear. The C-terminal domain of Fcj1 and the TOB complex are shown to interact. Both are important for determining cristae morphology. The results explain how crista junctions are positioned at the outer membrane, assigning novel functions to both Fcj1 and the TOB complex.

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 ).…”

“…These findings have prompted the hypothesis of a structural and functional connection between contact sites and crista junctions. The possibility of such an overlapping localization has been repeatedly addressed, although never comprehensively clarified (van der Klei et al , 1994 ;Perkins et al , 1997 ;Reichert and Neupert , 2002 ;Harner et al , 2011 ;K ö rner et al, 2012 ). Some studies have suggested that the integrity of crista junctions may depend on their anchoring to the outer mitochondrial membrane via mitofilin-containing contact sites (Harner et al , 2011 ;K ö rner et al, 2012 ;Ott et al , 2012 ).…”

“…The possibility of such an overlapping localization has been repeatedly addressed, although never comprehensively clarified (van der Klei et al , 1994 ;Perkins et al , 1997 ;Reichert and Neupert , 2002 ;Harner et al , 2011 ;K ö rner et al, 2012 ). Some studies have suggested that the integrity of crista junctions may depend on their anchoring to the outer mitochondrial membrane via mitofilin-containing contact sites (Harner et al , 2011 ;K ö rner et al, 2012 ;Ott et al , 2012 ). Along the same lines, downregulation of the SAM complex, one of the outer membrane interaction partners of mitofilin, was found to result in alterations of mitochondrial ultrastructure in human cultured cells and yeast ( K ö rner et al, 2012 ;Ott et al , 2012 ).…”

“…Mitofilin possesses an N-terminal mitochondrial targeting sequence followed by a transmembrane segment and a large domain exposed to the intermembrane space. The intermembrane space domain consists of at least two defined subdomains: an extended putative coiled-coil region and a short C-terminal mitofilin signature domain von der Malsburg et al , 2011 ;K ö rner et al, 2012 ;Zerbes et al , 2012 ). Mitofilins are ubiquitous mitochondrial proteins that share this domain organization from yeast to humans, whereas the mitofilin signature domain is the only part of the protein that exhibits strong conservation at the primary structure level across species K ö rner et al, 2012 ;Zerbes et al , 2012 ).…”

“…The intermembrane space domain consists of at least two defined subdomains: an extended putative coiled-coil region and a short C-terminal mitofilin signature domain von der Malsburg et al , 2011 ;K ö rner et al, 2012 ;Zerbes et al , 2012 ). Mitofilins are ubiquitous mitochondrial proteins that share this domain organization from yeast to humans, whereas the mitofilin signature domain is the only part of the protein that exhibits strong conservation at the primary structure level across species K ö rner et al, 2012 ;Zerbes et al , 2012 ). 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 ).…”