This paper reviews tiny proteins made by mitochondria, called mitochondrial‑derived peptides (MDPs), like humanin. It says these peptides can influence metabolism and may help with conditions such as Alzheimer’s, cancer, eye disease, heart disease, and diabetes. The authors note that a few genetic variations in humanin and another peptide are linked to cognitive decline and diabetes, hinting that these tiny proteins could be important for health, but most of the research is still early and many more peptides probably exist.

Mitochondrial-derived peptides (MDPs) are a novel class of bioactive microproteins that modify cell metabolism. The the eight MDPs that been characterized (e.g., humanin, MOTS-c, SHLPs1-6) attenuate disease pathology including Alzheimer's disease, prostate cancer, macular degeneration, cardiovascular disease, and diabetes. The association between disease and human genetic variation in MDPs is underexplored, although two polymorphisms in humanin and MOTS-c associate with cognitive decline and diabetes, respectively, suggesting a precise role for MDPs in disease-modification. There could be hundreds of additional MDPs that have yet to be discovered. Altogether, MDPs could explain unanswered biological and metabolic questions and are part of a growing field of novel microproteins encoded by small open reading frames. In this review, the current state of MDPs are summarized with an emphasis on biological and therapeutic implications.