Abstract
In eukaryotic cells, mitochondria host ancient essential bioenergetic and biosynthetic pathways. LYR (leucine/tyrosine/arginine) motif proteins (LYRMs) of the Complex1_LYR-like superfamily interact with protein complexes of bacterial origin. Many LYR proteins function as extra subunits (LYRM3 and LYRM6) or novel assembly factors (LYRM7, LYRM8, ACN9 and FMC1) of the oxidative phosphorylation (OXPHOS) core complexes. Structural insights into complex I accessory subunits LYRM6 and LYRM3 have been provided by analyses of EM and X-ray structures of complex I from bovine and the yeast Yarrowia lipolytica, respectively. Combined structural and biochemical studies revealed that LYRM6 resides at the matrix arm close to the ubiquinone reduction site. For LYRM3, a position at the distal proton-pumping membrane arm facing the matrix space is suggested. Both LYRMs are supposed to anchor an acyl-carrier protein (ACPM) independently to complex I. The function of this duplicated protein interaction of ACPM with respiratory complex I is still unknown. Analysis of protein-protein interaction screens, genetic analyses and predicted multi-domain LYRMs offer further clues on an interaction network and adaptor-like function of LYR proteins in mitochondria.
Highlights
In eukaryotic cells, mitochondria host ancient essential bioenergetic and biosynthetic pathways
These results suggest that LYRM1 takes part in a metabolic redox-dependent signaling pathway connected to mitochondrial biogenesis and homeostasis (PI3K, Akt/PKB pathway)
Nuclear-encoded LYRMs of eukaryotes are primarily mitochondrial proteins. They function as mitochondrial adaptor proteins and are accessory factors (LYR factors) controlling mitochondrial homeostasis
Summary
The LYR proteins (LYRMs) of the Complex1_LYR-like superfamily are exclusively found in eukaryotes. Other LYRMs have been identified as accessory subunits or assembly factors of mitochondrial OXPHOS complexes I, II, III and V, respectively, and to play a role in acetate metabolism [2]. II subunit SDHB and complex III assembly factor LYRM7/MZM1L carry L-Y-R(-like) sequences (Table 1, Supplemental Figure S1). The downstream phenylalanine of the LYR motif (Table 1) might play an important role in the function of LYRMs. Complex I accessory subunit LYRM6/NDUFA6 (yeast NB4M) from the yeast. It cannot be excluded that the soluble matrix LYRM6 might have extra functions, e.g., as a maturation factor of the Fe-S cluster containing central subunits increasing the abundance of complex I in mitochondrial membranes. There are indications that LYRMs are adaptor-like mitochondrial factors that promote the assembly and function of multi-subunit protein complexes
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