Known Roles
Some of the Many But Little Known Roles Mitochondria Play in Disease and Health
Table 1. An expanding understanding of mitochondrial function and human health.
Mitochondrial Function
ATP production: Mitochondria convert oxygen and nutrients into ATP (energy) through oxidative phosphorylation
Known or Potential Impact on Human Health
Diseases associated with impaired mitochondrial energy productions include: Leber hereditary optic neuropathy; Leigh syndrome; mitochondrial encephalomyopathy, lactic acidosis, and Stroke-like Episodes (MELAS); Kearns-Sayre syndrome; Myoclonic epilepsy and ragged-red fiber disease; Barth syn- drome; and various forms of mitochondrial myopathy; this list is specific to inherited disorders of oxidative phosphorylation and does not include how mitochondrial energy production disruptions contribute to overall health
Mitochondrial Function
Signal transduction: Mitochondria play a crucial role in signal transduction by acting as sensory organelles, detecting various cellular signals like metabolic changes and stress stimuli, integrating this information, and then producing output signals that can influence cell behavior, gene expression, and overall physiology through the release of molecules like calcium ions, reactive oxygen species (ROS), and metabolites
Known or Potential Impact on Human Health
Diseases associated with mitochondrial signal transduction dysfunction include: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, other neurodegenerative disorders, amyotrophic lateral sclerosis, MELAS, diabetes, cardiovascular disease, and certain cancers
Mitochondrial Function
Regulation of cellular metabolism: Mitochondria contribute to the regulation of cellular metabolic activity
Known or Potential Impact on Human Health
Diseases associated with mitochondrial regulation of cellular metabolism include: Type 2 diabetes, metabolic syndrome, cardiovascular diseases, Alzheimer’s disease, Parkinson’s disease, other neurodegenerative disorders, cancer, non-alcoholic fatty liver disease, and Leigh syndrome
Mitochondrial Function
Intracellular signaling: Mitochondria can store and release calcium ions, which contribute to signaling between cells
Known or Potential Impact on Human Health
Diseases associated with mitochondrial regulation of intra-cellular signaling include: Parkinson’s disease, Alzheimer’s disease, muscular dystrophy, type 2 diabetes, cardiovascular diseases, cancer, and certain developmental disorders
Mitochondrial Function
Programmed cell death: Mitochondria regulate programmed cell death (apoptosis) through the release of cytochrome c in response to apoptotic stimuli
Known or Potential Impact on Human Health
Diseases associated with abnormal mitochondrial regulation of apoptosis include: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, age-related macular degeneration, diabetic retinopathy, cardiovascular diseases, and certain cancers
Mitochondrial Function
Biomolecule synthesis: Mitochondria act as a central hub for the production of building blocks like amino acids, fatty acids & cholesterol, nucleotides, and glucose and heme synthesis
Known or Potential Impact on Human Health
Diseases associated with abnormal mitochondrial regulation of biomolecule synthesis include: Leigh syndrome, MELAS, sensorineural hearing loss, mitochondrial myopathy, hypertrophic cardiomyopathy, Alzheimer’s disease, Niemann-Pick type C disease, fatty liver disease, sideroblastic anemias, porphyria’s, type 2 diabetes, and certain cancers
Table 2. An expanding understanding of mitochondrial function and human health.
Tissue- or Cell-Specific Mitochondrial Function
Heat production: In brown adipose tissue, mitochondria are involved in thermogenesis
Known or Potential Impact on Human Health
Diseases primarily associated with mitochondrial regulation of thermogenesis include: obesity, type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease
Tissue- or Cell-Specific Mitochondrial Function
Detoxification: In liver cells, mitochondria contain enzymes that allow them to detoxify ammonia, a waste product of protein synthesis
Known or Potential Impact on Human Health
The primary disease associated with mitochondrial regulation of liver ammonia detoxification is hepatic encephalopathy
Tissue- or Cell-Specific Mitochondrial Function
Neurotransmission: In neurons, mitochondria are involved in each stage of neurotransmission including synthesis and storage of neurotransmitters, trafficking and recycling of synaptic vesicles, and the release of neurotransmitters
Known or Potential Impact on Human Health
Diseases associated with mitochondrial regulation of neuro-transmission primarily include: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and certain psychiatric conditions like bipolar disorder and depression
Tissue- or Cell-Specific Mitochondrial Function
Stem cell reprogramming: Mitochondria contribute to the maintenance of pluripotency, differentiation, and reprogramming of induced pluripotent stem cells; mitochondrial oxidative phosphorylation is necessary for cell differentiation, and transition mitochondrial oxidative metabolism to glycolysis may be required for stem cell reprogramming
Known or Potential Impact on Human Health
Diseases associated with mitochondrial regulation of stem cell reprogramming include: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis; other potential disease areas include cancer due to abnormal stem cell proliferation and aging-related diseases due to declining mitochondrial function in stem cells
Tissue- or Cell-Specific Mitochondrial Function
Innate immunity regulation: In immune cells, mitochondria participate in a broad range of innate immune pathways, including RIG-I-like receptor signaling, antibacterial immunity, and the sterile inflammatory response
Known or Potential Impact on Human Health
Diseases associated with mitochondrial regulation of innate immunity include: Systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, Sjögren’s syndrome, neurodegenerative diseases like amyotrophic lateral sclerosis, and certain fibrotic diseases
A Great Deal Is Starting To Be Known About The “What” Of Mitochondria, but the path toward understanding the ”why” relating to mitochondrial function in health and disease is still in its infancy due to a lack of funding and strategic programming. However, the spiraling costs of health care, inappropriate diet, and a lack of cures across the spectrum is leading to rising incidence of diabetes and obesity, cardiac issues, psychiatric disorders. Failure to address chronic fatigue, long Covid and the range of neurodegenerative diseases calls on new bold strategic steps. These and other issues, like the mitochondrial degradation in microgravity, require new commitments.
MITOS Dialog-Based Community Building will manage multiple strands of dialog within the mitochondrial communities and between the mitochondrial community and the various branches of medicine, health, basic biology, patients and the interested public.