Muscle Mitochondria Up in Smoke: A Review on Cigarette Smoke-induced Adaptations to Mitochondrial Energy Flux Through OXPHOS in Skeletal Muscle

Stephen Decker^1*Alexs Matias²Sean Bannon³

• ¹The University of Utah, Salt Lake City, United States
• ²University of Delaware, Newark, Delaware, United States
• ³University of Massachusetts Amherst, Amherst, Massachusetts, United States

Cigarette smoke, a global health hazard, contains thousands of toxic compounds that impact biological systems, including skeletal muscle mitochondria. This review examines how cigarette smoke impairs mitochondrial energy flux through oxidative phosphorylation (OXPHOS), focusing on mechanisms such as complex I inhibition, increased proton leak, and reactive oxygen species (ROS) generation. These adaptations lead to impaired ATP production, reduced exercise capacity, and altered muscle function, particularly under conditions of high oxygen demand during physical activity. We discuss the implications of these findings for exercise physiology and propose potential therapeutic strategies, including mitochondrial-targeted antioxidants like MitoQ and Mito-TEMPO. Additionally, we highlight gaps in knowledge, such as the interaction between smoking, physical inactivity, and mitochondrial dysfunction, and call for human studies to assess the acute and chronic effects of cigarette smoke on skeletal muscle bioenergetics. This work underscores the need for integrated interventions to mitigate cigarette smokeinduced mitochondrial impairments, ultimately improving health and exercise outcomes in affected populations.