Mitochondrial disease

Mitochondrial disease is a group of genetic disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of food molecules into the ATP that powers most cell functions.

Mitochondrial diseases take on unique characteristics both because of the way the diseases are often inherited and because mitochondria are so critical to cell function. A subclass of these diseases that have neuromuscular symptoms are known as mitochondrial myopathies. Additionally, different paradigms like intermittent fasting can improve mitochondrial health and contribute in longevity.

Types

Mitochondrial disease can manifest in many different ways whether in children or adults. Examples of mitochondrial diseases include:

Mitochondrial myopathy

Maternally inherited diabetes mellitus and deafness (MIDD)

While diabetes mellitus and deafness can be found together for other reasons, at an early age this combination can be due to mitochondrial disease, as may occur in Kearns–Sayre syndrome and Pearson syndrome

Leber's hereditary optic neuropathy (LHON)

LHON is an eye disorder characterized by progressive loss of central vision due to degeneration of the optic nerves and retina (apparently affecting between 1 in 30,000 and 1 in 50,000 people); visual loss typically begins in young adulthood

Leigh syndrome, subacute necrotizing encephalomyelopathy

after normal development the disease usually begins late in the first year of life, although onset may occur in adulthood

a rapid decline in function occurs and is marked by seizures, altered states of consciousness, dementia, ventilatory failure

Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)

progressive symptoms as described in the acronym

dementia

Myoneurogenic gastrointestinal encephalopathy (MNGIE)

gastrointestinal pseudo-obstruction

neuropathy

MERRF syndrome

progressive myoclonic epilepsy

"Ragged Red Fibers" are clumps of diseased mitochondria that accumulate in the subsarcolemmal region of the muscle fiber and appear when muscle is stained with modified Gömöri trichrome stain

short stature

hearing loss

lactic acidosis

exercise intolerance

MELAS syndrome, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes

Mitochondrial DNA depletion syndrome

Cancer: While the cancer cells prefer Warburg effect however efficient mitochondrial maintenance remains crucial for tumor resilience, redox regulation, and avoidance of cell death. Tumor cells exhibit metabolic heterogeneity, shifting between glycolysis and mitochondrial oxidative phosphorylation to meet energy demands and support growth, especially during metastasis. Key bioenergetic parameters such as oxygen flux, proton leakage, membrane potential, extracellular acidification rate (ECAR), and proton-motive force are examined as “sub-domains” that tumors may regulate to promote survival and evade apoptosis.