Polymorphic mitochondrial peptides function as olfactory cues for individual recognition

One of our important present findings is that the strain-specific mitochondrial peptides that differ from those of the mating male’s strain by a single amino acid substitution can elicit pregnancy block. However, no study to date has demonstrated differential responses of vomeronasal sensory neurons (VSNs) to the strain-specific mitochondrial peptides, and much more work needs to be done to determine how VSNs and their receptors discriminate mitochondrial peptide sequences and which ligand features are critical for sensory neuron activation. It has been shown that humans have the ability to detect and evaluate major histocompatibility complex (MHC) peptide ligands in body odor. For example, women prefer the odor of shirts worn by men with different MHC alleles to those of men with more closely matching MHC alleles. This raises the interesting question whether humans are able to perceive polymorphic mitochondrial peptides. What is it about?For most mammals, olfaction plays an important role in individual recognition. The social odors secreted by individuals are complex variable mixtures that are still poorly understood. We discovered a new class of social odors for individual recognition–that is, polymorphic mitochondrial peptides that are maternally inherited and can be used to convey strain-specific information among individual mice.Why is it important?Here we show that the unfamiliar (non-self) variants of non-formylated, but not N-formylated, mitochondrial peptides differing by a single amino acid residue from a familiar (self) variant function as strain-specific chemosensory cues and thus differentially induce a strain-selective pregnancy block. Our findings emphasize that the mitochondrial peptides are naturally released from a mouse and can form part of the suite of cues for the recognition of strain differences. Our findings also emphasize that pregnancy-blocking odors in the urine are maternally inherited, as evidenced by the production of reciprocal sons from two inbred strains and our test of their urine’s ability to block pregnancy. Such mitochondrial peptides that can signal individual information may be of importance in other vertebrate species, including humans.