Mitochondria: a central target for sex differences in pathologies

Abstract

It is increasingly acknowledged that a sex and gender specificity affects the occurrence, development, and consequence of a plethora of pathologies. Mitochondria are considered as the powerhouse of the cell because they produce the majority of energy-rich phosphate bonds in the form of adenosine tri-phosphate (ATP) but they also participate in many other functions like steroid hormone synthesis, reactive oxygen species (ROS) production, ionic regulation, and cell death. Adequate cellular energy supply and survival depend on mitochondrial life cycle, a process involving mitochondrial biogenesis, dynamics, and quality control via mitophagy. It appears that mitochondria are the place of marked sexual dimorphism involving mainly oxidative capacities, calcium handling, and resistance to oxidative stress. In turn, sex hormones regulate mitochondrial function and biogenesis. Mutations in genes encoding mitochondrial proteins are the origin of serious mitochondrial genetic diseases. Mitochondrial dysfunction is also an important parameter for a large panel of pathologies including neuromuscular disorders, encephalopathies, cardiovascular diseases (CVDs), metabolic disorders, neuropathies, renal dysfunction etc. Many of these pathologies present sex/gender specificity. Here we review the sexual dimorphism of mitochondria from different tissues and how this dimorphism takes part in the sex specificity of important pathologies mainly CVDs and neurological disorders.

An energetic view of stress: Focus on mitochondria

“…Indeed, even if all mitochondria and the mtDNA are uniquely inherited from the mother (Giles et al, 1980), differences in protein composition and function are acquired during development and as a result, multiple facets of mitochondrial biology differ by sex in adult animals (Ventura-Clapier et al, 2017). This is, in part, due to the fact that sex hormones regulate mitochondrial function and biogenesis (Gaignard et al, 2017).…”

Sex differences in cancer mechanisms

“…Mitochondria exhibit a strong sex-specific behavior as they are exclusively maternally inherited. A vast body of literature describes tissue and cell-specific sex differences in mitochondria morphology, function, and oxidative stress regulation [193]. Here, we will focus specifically on sex differences in the brain; however, since sex differences in mitochondria have been reported in tissues throughout the body, including liver, cerebral arteries, white and brown adipose tissue, pancreas, muscle, and heart, our discussion likely applies to multiple cancer types.…”

Sex Differences in Early Embryogenesis: Inter‐Chromosomal Regulation Sets the Stage for Sex‐Biased Gene Networks

“…Moreover, mitochondrial function varies in adult males and females but the origin of these differences is unknown. [116,117] Acknowledging these gaps should lend strong impetus for bridging them with detailed, mechanistic studies.…”