This mouse study mapped where a humanin‑like peptide gene (Gm20594) and the classic mitochondrial humanin gene (Mtrnr1) are made, finding they’re especially high in brown fat and gut and rise when cells grow more mitochondria, but it doesn’t test any treatments or human effects.

Mitochondrial-derived peptides (MDPs) such as MOTS-c and humanin have been studied for their cytoprotective functions. In mice, humanin-encoding <i>Mtrnr2</i> is a mitochondrial pseudogene, and the humanin-like peptide is encoded by the nuclear <i>Gm20594</i> gene. However, endogenous tissue-specific expression profiles of <i>Gm20594</i> have not yet been identified. <i>Mtrnr1</i> and <i>Gm20594</i> expression was profiled via reverse transcription using only oligo(dT) primers from tissues of C57BL6/J mice. To analyze altered expression upon mitochondrial biogenesis, C2C12 myocytes and brown adipocytes were differentiated. Mitochondrial DNA copy numbers were quantified for normalization. Both <i>Mtrnr1</i> and <i>Gm20594</i> were highly expressed in brown adipose tissue. When normalized against mitochondrial content, <i>Mtrnr1</i> was identified as being highly expressed in the duodenum, followed by the jejunum. In models of mitochondrial biogenesis, both <i>Mtrnr1</i> and <i>Gm20594</i> were upregulated during myocyte and brown adipocyte differentiation. Increased <i>Mtrnr1</i> expression during brown adipocyte differentiation remained significant after normalization against mitochondrial DNA copy number, whereas myocyte differentiation exhibited biphasic upregulation and downregulation in early and late phases, respectively. Nuclear-encoded <i>Gm20594</i> showed similar expression patterns of mitochondrial-encoded <i>Mtrnr1</i>. Brown adipose tissue presented the highest basal expression levels of <i>Gm20594</i> and <i>Mtrnr1</i>. When normalized against mitochondrial DNA copy number, gut tissues exhibited the highest expression of <i>Mtrnr1</i>. Upregulation of <i>Mtrnr1</i> during mitochondrial biogenesis is independent of mitochondrial content.