Novel Insights into Mitochondrial DNA: Mitochondrial Microproteins and mtDNA Variants Modulate Athletic Performance and Age-Related Diseases

Genes (Basel). 2023 Jan 21;14(2):286. doi: 10.3390/genes14020286.

Abstract

Sports genetics research began in the late 1990s and over 200 variants have been reported as athletic performance- and sports injuries-related genetic polymorphisms. Genetic polymorphisms in the α-actinin-3 (ACTN3) and angiotensin-converting enzyme (ACE) genes are well-established for athletic performance, while collagen-, inflammation-, and estrogen-related genetic polymorphisms are reported as genetic markers for sports injuries. Although the Human Genome Project was completed in the early 2000s, recent studies have discovered previously unannotated microproteins encoded in small open reading frames. Mitochondrial microproteins (also called mitochondrial-derived peptides) are encoded in the mtDNA, and ten mitochondrial microproteins, such as humanin, MOTS-c (mitochondrial ORF of the 12S rRNA type-c), SHLPs 1-6 (small humanin-like peptides 1 to 6), SHMOOSE (Small Human Mitochondrial ORF Over SErine tRNA), and Gau (gene antisense ubiquitous in mtDNAs) have been identified to date. Some of those microproteins have crucial roles in human biology by regulating mitochondrial function, and those, including those to be discovered in the future, could contribute to a better understanding of human biology. This review describes a basic concept of mitochondrial microproteins and discusses recent findings about the potential roles of mitochondrial microproteins in athletic performance as well as age-related diseases.

Keywords: MOTS-c; age-related diseases; athletic performance; genetic polymorphism; injury; microprotein; mitochondrial-derived peptide; small open reading frame.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Actinin / genetics
  • Aging
  • Athletic Injuries*
  • Athletic Performance*
  • DNA, Mitochondrial / genetics
  • Humans
  • Micropeptides
  • Mitochondria / genetics
  • Peptides / genetics

Substances

  • DNA, Mitochondrial
  • Peptides
  • ACTN3 protein, human
  • Actinin