Mitochondria and Disease
Mitochondria have been called the most successful life form on the planet, in large measure because nearly all animal and plant cells contain scores of mitochondria. During evolution, an ancestral cell formed a working relationship with a free-living “bacterium-like” organism. This co-dependent relationship allowed these ancestral cells to produce energy, in the form of high-energy phosphate bonds of adenosine triphosphate (ATP), more efficiently than other cells. This selective advantage fostered development of multicellular organisms, and as a remnant of its past life, each mitochondrion contains a “private” set of genes for the production of proteins that are critical to the process of cellular energy production.
However, such heavy reliance on mitochondrial energy production has its costs. Mitochondria normally replicate independently of cell division, becoming senescent and being replaced by fission every few weeks. In this way, oxidative and other damage to the mitochondrial genome can gradually accumulate as we age, leading to a gradual decline in mitochondria efficiency. If we live long enough, mitochondrial function eventually deteriorates resulting in diminished energy production and accelerated free radical production that can initiate a number of late-onset diseases. Severe deficits in mitochondrial function inevitably undermine cellular integrity, especially in highly energy demanding tissues such as brain, retina, heart and other muscles.
Central role mitochondria
They play in maintaining cell life and death, it should not be surprising that mitochondrial failure is a disaster for most cells. Unfortunately, this is all too true, and a host of mitochondrial abnormalities, many due to well-described mutations in the mitochondrial DNA, cause dozens of rare, but very debilitating human diseases. Many of these mitochondrial diseases are known best by their acronyms, such as MELAS and MERRF, and links to some of the websites available for education and support groups are provided in the Resources section. It is significant that, in addition to muscular and metabolic abnormalities, including diabetes, many of these mitochondrially inherited diseases also have neurodegenerative and cognitive components, such as blindness, deafness and other central nervous system impairment.
In addition, because they play so many important roles in cellular metabolism, mitochondria also become a focal point for break down under pathological conditions. For example, under conditions of tissue ischemia, such as occurs during a stroke or heart attack, normally functioning mitochondria accumulate excess calcium and increase their production of reactive free radicals. This in turn imperils mitochondrial integrity, and endangers the cell’s viability. In this way, treatments designed to stabilize normal mitochondria under pathological circumstances, as opposed to treating dysfunctional mitochondria, offer novel approaches to moderating injury in a number of situations, including stroke and myocardial infarction.