The energy produced by mitochondria is used in many fundamental signalling and metabolic pathways, impacting most areas of cell biology and health
Almost every cell in our body contains hundreds of tiny power plants called mitochondria that are responsible for approximately 90% of the energy demands of cells.
Mitochondria are unique organelles: connected in a dynamic network, they use oxygen to convert carbohydrates, free fatty acids and proteins into Adenosine Triphosphate (ATP), a chemical compound that provides energy to almost every chemical reaction in our cells. This energy is used in many fundamental signalling and metabolic pathways (including steroid hormone production, proliferation and apoptosis cell decisions, cholesterol metabolism, and the process and synthesis of key metabolites) impacting most areas of cell biology and health.
These organelles are unique in another aspect: they are the only human organelle that harbors its own genome – termed mitochondrial DNA, or mtDNA. Over the course of evolution, mitochondria have evolved to enable humans to adapt to multiple metabolic requirements. Therefore, over time, the mtDNA of these organelles have amassed single nucleotide polymorphisms, SNPs, some of which enable nuanced differences in bioenergetics and mitochondrial function. These SNPs define different human haplogroups, groups with mitochondrial sequence differences that represent major branch points defined by human migration out of Africa and population of the globe. A subset of these SNPs, these small changes of the mitochondrial genome (adaptive polymorphisms), have enabled us to live and thrive in areas as diverse as the cold Arctic circle to the Saharan desert.
The human body requires vast amounts of ATP for healthy function, especially an extremely active organs such as our brain, heart and muscle, as well as cells requiring bursts of high activity, such as immune cells. Mitochondrial dysfunction can affect anyone from birth to late adulthood and can be multi-systemic or organ-specific. Deterioration in mitochondrial functionality can be caused by genetic or environmental causes.
Without healthy mitochondria, cells and organs malfunction leading to devastating multisystemic mitochondrial diseases. Point mutations and deletions in mtDNA are known to occur in certain primary mitochondrial diseases, as well as to accumulate with age, and can have profound effects on the function of multiple organ systems.
In diseases involving mutations or deletions of the mtDNA, mutated and wild-type (normal) mtDNA molecules co-exist in the same cell, a state defined as heteroplasmy. Relative level of mutated to wild-type mtDNA is known to correlate with disease severity in that organ.
In addition to heteroplasmy levels, there are multiple other parameters that affect the severity of mitochondrial diseases, including the total mtDNA copy number, mitochondrial haplogroup and nuclear background.
Stewart & Chinnery, 2015 Nature Reviews Genetics