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Mutations in highly conserved genes encoding components of the electron transport chain (ETC) provide valuable insights into the mechanisms of oxidative stress and mitochondrial ROS (mtROS) in a wide range of diseases, including cancer, neurodegenerative disorders, and aging. This review explores the structure and function of the ETC in the context of its role in mtROS generation and regulation, emphasizing its dual roles in cellular damage and signaling. Using Caenorhabditis elegans as a model organism, we discuss how ETC mutations manifest as developmental abnormalities, lifespan alterations, and changes in mtROS levels. We highlight the utility of redox sensors in C. elegans for in vivo studies of reactive oxygen species, offering both quantitative and qualitative insights. Finally, we examine the potential of C. elegans as a platform for testing ETC-targeting drug candidates, including OXPHOS inhibitors, which represent promising avenues in cancer therapeutics. This review underscores the translational relevance of ETC research in C. elegans, bridging fundamental biology and therapeutic innovation. [ABSTRACT FROM AUTHOR]

A myocardial oxygen-supply-demand mismatch (type-II myocardial ischemia) is a common cause of perioperative complications. Patients with compromised coronary vasculature are most at risk for deoxygenation, as routinely used anesthetics and rapid changes in blood gases trigger changes in coronary blood supply and myocardial workload. Often males have a higher preoperative risk assessment for cardiovascular complications, yet females are reported to have almost an equal complication rate for type-II ischemia despite not being identified as high-risk. Even traditional diagnostic imaging tests designed to detect inducible ischemia are based on regional variations in myocardial blood flow (MBF) linked to stenoses in epicardial vessels, allowing little insight to possible balanced ischemia/microvascular disease and local oxygen-supply-demand balance. This may contribute to underestimation of cardiovascular disease in female patients. With newer cardiovascular magnetic resonance (CMR) imaging techniques, MBF can be interrogated for absolute blood flow per millimeter detecting microvascular disease. Myocardial oxygenation can be separately quantified with oxygenation-sensitive CMR. We applied these developing CMR techniques to gain insight into potential sex-based differences for induced myocardial deoxygenation under pharmacological and changing-blood-gas stimuli in patients with suspected ischemic heart disease. Eighty patients (n=80, 70% male) with suspected ischemic heart disease referred for a clinical CMR exam were prospectively recruited. The standard clinical assessment of inducible ischemia was performed with perfusion imaging under pharmacological stress protocol to assess regional variation in perfusion under hyperemia (400µg regadenoson and 0.075mmol/kg contrast agent). These perfusion sequences were analyzed for absolute MBF in mL/g/min using a research-based software. Oxygenation-sensitive images were acquired during the pharmacological stress, and during a breathing maneuver stimulus. For the latter, patients breathed deeply and rapidly for 60s to induce hypocapnia, followed by 30s of apnea to induce hypercapnia. The %-change in myocardial oxygenation for both stimuli was calculated. Deoxygenation was defined as a drop in signal (percent change <0%). Under pharmacological stress, clinical assessments reported visual perfusion deficits in 7/56 (13%) male patients and none (0/24, 0%) in females. As a more sensitive analysis of microvascular dysfunction, quantitative MBF analysis showed that 35% of the females had poor MBF (<1.5mL/g/min) under stress, as did 51% of males (p=0.097). However, global myocardial oxygenation responses did not differ between sexes (F:5.7±7.2%, M:4.5±6.5%, p=0.49). Furthermore, the same proportion of females experienced global deoxygenation as males (F:22%, M:25%, p=0.71) under pharmacologic stress. During the blood-gas stimulus induced by breathing maneuvers, females also showed the same myocardial oxygenation response as males (F:0.9±7.1%, M:0.7±9.2%, p=0.92), with the same proportion yielding an inducible myocardial deoxygenation (F:44%, M:43%, p=0.94). Oxygenation-sensitive CMR in a diagnostic setting demonstrates that in awake patients with suspected ischemic heart disease, females are just as likely to have inducible myocardial oxygenation deficits as males under both pharmacological hyperemia and induced changes in blood gases. Thus, it is important not to underestimate female risk of inducible myocardial deoxygenation. An interdisciplinary approach using modern imaging techniques may help to better understand the role of female heart disease and potential perioperative ischemia. [ABSTRACT FROM AUTHOR]