Mitochondria constitute the major energy plant of the cell; genetic defects of mitochondrial bioenergetics cause an astonishingly wide spectrum of disorders. As the site of oxidative phosphorylation, mitochondria are the chief consumers of intracellular oxygen and thus are the main source of reactive oxygen species (ROS). The traditional view of ROS production being unregulated and their targets being random was challenged by recent evidence; ROS are now being appreciated to have beneficial effects like signaling, the in vivo importance of which has not been adequately investigated.

The adaptability of skeletal muscle mitochondria to various stressors and stimuli is well-known as these organelles are highly dynamic. However, when faced with severe and sustained mitochondrial dysfunction, these mechanisms are insufficient, leading to mitochondrial myopathies that cause significant muscular dysfunction. I will be introducing and discussing the importance of ROS signaling in two different myopathy mouse models: (i) Mitochondrial respiratory deficiency model, COX15^mko, and a novel (ii) Mitochondrial translation deficiency model, DARS2^mko. Currently, ROS-lowering interventions are widely proposed as an anti-aging strategy in humans and used widely as therapy in some diseases. However, reducing the ‘good/signaling ROS’ might be detrimental in some cases.

Cells have developed processes for monitoring the integrity of their mitochondrial network to finetune their current conditions to overcome environmental insults and respond to physiological cues. If mitochondrial function declines, mitochondrial stress responses (MSRs) are activated to promote the repair and recovery of this network and maintain cellular function. Additionally, I will focus on how the induction of major MSRs correlate with mitochondrial myopathy and disease progression, examining the potential existence of tissue-specific responses.