Mitochondrial LYRM (leucine/tyrosine/arginine motif) proteins are members of the Complex1_LYR-like superfamily. Individual LYRM proteins have been identified as accessory subunits or assembly factors of mitochondrial OXPHOS (oxidative phosphorylation) complexes I, II, III and V respectively, and they play particular roles in the essential Fe-S cluster biogenesis and in acetate metabolism. LYRM proteins have been implicated in mitochondrial dysfunction, e.g. in the context of insulin resistance. However, the functional significance of the common LYRM is still unknown. Analysis of protein-protein interaction screens suggests that LYRM proteins form protein complexes with phylogenetically ancient proteins of bacterial origin. Interestingly, the mitochondrial FAS (fatty acid synthesis) type II acyl-carrier protein ACPM associates with some of the LYRM protein-containing complexes. Eukaryotic LYRM proteins interfere with mitochondrial homoeostasis and might function as adaptor-like 'accessory factors'.