Work

Mitochondrial-derived microproteins in lung disease: insights and implications

Year: 2026

Type: article

Abstract: As bioactive microproteins, mitochondrial-derived microproteins (MDPs) are encoded within the small open reading frames of mitochondrial DNA. MDPs have been shown to be altered in a number of disease states and have mitochondrial, nuclear, and extracellular actions. Most published work on MDPs has focused on MOTS-c and Humanin's actions in tissues with high mitochondrial density (heart, skeletal muscle, and brain) or in disease states of advanced age-Alzheimer's, cancer, and cardiovascular disease. This review aims to highlight the existing gaps in knowledge related to MDPs' role in lung homeostasis and disease-including acute lung injury, chronic obstructive pulmonary disease, allergic asthma, and pulmonary fibrosis. The increasingly recognized role of MDPs in nonpulmonary diseases sheds light on the importance of more investigations of MDPs, their clinical and mechanistic roles, and their therapeutic potential for pulmonary diseases.

Source: American Journal of Physiology-Lung Cellular and Molecular Physiology

DOI: 10.1152/ajplung.00369.2025

Authors: Molly Behan, Kelvin Yen, Pinchas Cohen, Corrine R. Kliment

Institutions: University of Pittsburgh, University of Southern California

Language: English

Topic: Mitochondrial Function and Pathology

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: Burroughs Wellcome Fund, National Heart, Lung, and Blood Institute