The aim of this study was to describe the stability of proteins encoded in mtDNA, which are part of the OXPHOS system, in different model organisms and to define why certain proteins are more prone to be unstable than others. The in silico analyses involved 155 reference sequences of all proteins encoded in the mitochondrial DNA in twelve model organisms representing different phylogenetic groups. The amino acid sequences of the proteins were taken from the GenPept database. The bioinformatic analyses were performed in the ProtParam program. Thirty-eight of the 155 analyzed proteins exhibited instability. The greatest numbers of unstable mitochondrial proteins were detected in H. sapiens and A. mexicanum and the lowest levels were found in C. elegans. ND1 and ATP8 were the most unstable mitochondrial proteins. Proteins COX1 and COX3 did not exhibit instability in the examined group of organisms. The highest instability index values were recorded in the case of protein ATP8. Protein ND1 turned out to be stable in the representatives of the class invertebrates. The preliminary results of the pioneer investigations indicate that the type and number of unstable proteins encoded in mtDNA was species specific. Protein instability in lower organisms may be associated with resistance to oxidative stress. In higher organisms, in turn, protein instability may be related to the physiological production of free oxygen radicals, which play multiple roles in metabolic processes. The phenomenon of instability in the respiratory chain proteins may have a strategic function although it appears to be detrimental to the stability of the protein structure per se.