Mitochondrial Open Reading Frame of the 12S rRNA Type-c: Potential Therapeutic Candidate in Retinal Diseases

Antioxidants (Basel). 2023 Feb 18;12(2):518. doi: 10.3390/antiox12020518.


Mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is the most unearthed peptide encoded by mitochondrial DNA (mtDNA). It is an important regulator of the nuclear genome during times of stress because it promotes an adaptive stress response to maintain cellular homeostasis. Identifying MOTS-c specific binding partners may aid in deciphering the complex web of mitochondrial and nuclear-encoded signals. Mitochondrial damage and dysfunction have been linked to aging and the accelerated cell death associated with many types of retinal degenerations. Furthermore, research on MOTS-c ability to revive oxidatively stressed RPE cells has revealed a significant protective role for the molecule. Evidence suggests that senescent cells play a role in the development of age-related retinal disorders. This review examines the links between MOTS-c, mitochondria, and age-related diseases of the retina. Moreover, the untapped potential of MOTS-c as a treatment for glaucoma, diabetic retinopathy, and age-related macular degeneration is reviewed.

Keywords: MOTS-c; age-related macular degeneration; diabetic retinopathy; glaucoma; mitochondrial dysfunction.

Publication types

  • Review

Grants and funding

This work was supported by the Discovery Eye Foundation, Polly and Michael Smith, Iris and B. Gerald Cantor Foundation, and National Eye Institute R01 EY027363 (MCK).