For Patients & Providers

Mitochondria, often described as the “powerhouse of the cell”, are responsible for approximately 90% of energy production in human cells.¹ These “powerhouses” are found in all human cells other than red blood cells.² Mitochondria produce energy through the conversion of food into adenosine triphosphate, or ATP.² This happens through a series of reactions, controlled by the electron transport chain, within the inner folds of the mitochondria.² In normal mitochondria, the inner mitochondrial membrane is highly folded, creating curves, called cristae.³ The cristae house the electron transport chain, which is composed of five protein complexes responsible for mitochondrial ATP production.³ Cardiolipin, a phospholipid found only in the inner mitochondrial membrane, is responsible for establishing the cristae architecture and optimizing the function of the electron transport chain for ATP generation.⁴ Dysfunctional mitochondria produce less ATP and increased unhealthy levels of reactive oxygen species, or ROS, which leads to oxidative stress.² Although low levels of ROS are normal and important for the cell, high levels of ROS can damage cardiolipin, thereby disrupting the structure of the inner mitochondrial membrane and triggering a cycle of increasing ROS generation that can lead to the inflammation, fibrosis, senescence and cell death implicated in many human diseases.⁵ Mitochondrial dysfunction characterizes numerous inherited rare diseases – collectively known as primary mitochondrial diseases – that arise from over 250 different genetic mutations.⁶ These include primary mitochondrial myopathy, Barth syndrome, and Leber’s hereditary optic neuropathy.^7-8 Mitochondrial dysfunction is also involved in a wide range of common age-related diseases, such as dry age related macular degeneration.^9-10 As the body’s main source of energy production, mitochondria are critical for normal organ function, particularly with respect to high energy demanding organ systems such as skeletal muscle, eye, brain, heart and kidney.^10-12 Patients with mitochondrial disease often experience functional deficit in three or more of these organ systems.^11-12

The term mitochondrial disease or disorder generally refers to a defect which exists somewhere along the energy building pathway.^2,12,35 Mitochondrial diseases are typically classified and named either after the specific genetic defect (e.g. POLG mutation) or the cluster of symptoms associated with the disease (e.g. MELAS: Mitochondrial Encephalopathy, lactic acidosis, stroke, or LHON: Leber’s hereditary optic neuropathy).^2,12,35 Some mitochondrial disorders are named after the clinician who first identified the disease (i.e. Leigh syndrome, Barth syndrome).^36-37 Regardless of the name, the term mitochondrial disease is an umbrella term that encompasses many specific conditions caused by mitochondrial defects. ^2,12,35