Mitochondrial Dysfunction 

An Overview of Mitochondrial Dysfunction 

Mitochondrial dysfunction is often described as an energy problem, but this captures only one aspect of a much broader process. Mitochondria continually adjust energy production to cellular demand while coordinating redox and calcium signalling, maintaining mitochondrial proteins and DNA, and removing components that can no longer be repaired.[1–7] Dysfunction develops when these systems become less able to adapt, recover, or maintain mitochondrial quality. The consequences may become most apparent during exercise, illness, or aging, when physiological demand rises and mitochondrial reserve is tested.[6–10] 

Mitochondrial abnormalities are observed across many diseases of aging, including neurodegenerative, cardiometabolic, cardiovascular, and musculoskeletal disorders.[2,6,8,9]  Mitochondrial phenotypes differ by tissue, disease, and stage of progression, making it difficult to assign mitochondrial dysfunction a single position in the pathological sequence. It may precede overt disease, develop in response to another cellular disturbance, or become increasingly important as pathology advances. Rather than functioning solely as a cause or consequence, mitochondrial dysfunction can become part of a feedback loop in which declining mitochondrial performance increases cellular stress and vulnerability, while the disease environment places further pressure on mitochondrial function.[8–10]