Mitochondrial-Derived Microproteins in Lung Disease: Insights and Implications

As bioactive microproteins, Mitochondrial-Derived-MicroProteins (MDPs) are encoded within the small open reading frames (sORFs) 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 MDP’s 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, 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 (ALI), Chronic Obstructive Pulmonary Disease (COPD), allergic asthma (AA) and Pulmonary Fibrosis (PF). The increasingly recognized role of MDPs in non-pulmonary diseases sheds light on the importance of more investigations of MDPs, their clinical and mechanistic roles, and their therapeutic potential for pulmonary diseases.