Table 1.

The molecular causes of mitochondrial dysfunction in various organs in the body.

Organ	Causes of Mitochondrial Dysfunction	Affected Genes/Proteins	Anticipated Disease State	Reference
Brain	Excessive accumulation of calcium in the mitochondrial matrix Opening of mitochondrial permeability transition pore Release of cytochrome C leading to activation of apoptosis Dysfunction in fission and fusion activities in mitochondria	Cyclophilin D (Cyp D) Cytochrome C (Cyt C) Mitofusin (Mfn) Dynamin-related protein1 (Drp1) Optic atrophy mitochondrial protein (OPA)	Traumatic brain injury (TBI) Alzheimer’s disease Parkinson’s disease Huntington’s disease Ischemic stroke	[110]
Liver	Inner mitochondrial lesions Dynamic alterations in mitochondria Lower levels if respiratory chain complex enzymes Inability to synthesize ATP	Nuclear factor- κB (NF- κB) I kappa B-kinase (IKK-α,β,γ) Stimulation of Interferon genes (STING) TANK binding kinase 1 (TBK1) Interferon regulatory factors (IRF3, IRF7)	Non-alcoholic fatty liver disease Alcoholic fatty liver disease Drug-associated fatty liver disease Hepatitis B Hepatitis C	[111]
Lungs	Increased concentration of iron mitochondria Abnormal metabolic activity due to excessive mtROS production Decrease in mitochondrial number and function	Mammalian target of rapamycin (mTOR) Peroxisome proliferator- activated receptor gamma coactivator 1-alpha (PGC-1α) Angiotensin converting enzyme 2 (ACE2) Tumor necrosis factor-α (TNF-α) Interleukin-6 (IL-6) Matrix metalloproteinase 2 (MMP2) Transforming growth factor-β (TGF-β)	Cystic fibrosis Asthma Pneumonia Tuberculosis Lung cancer Chronic obstructive pulmonary disease (COPD)	[112]
Eye	Defects in mitochondrial respiratory chain subunit complex I enzymes Deletion of mitochondrial DNA Fragments in mitochondrial network Loss of membrane potential Unproper arrangement cristae structure of optic nerve mitochondria	OPA 1 and 3 Thymidine phosphoryase (TYMP) Adenine nucleoside translocator 1 (ANT1) Twinkle mtDNA helicase (PEO1) DNA polymerase subunit gamma 1 (PLOG1)	Dominant optic atrophy (DOA) Leber Hereditary optic neuropathy (LHOA) Chronic progressive external ophthalmoplegia (CPEO) Pigmentary retinopathy	[113]
Skeletal system	Lower levels of mitochondrial enzyme production Decreased ATP production Decline in mitochondrial density Lower protein levels in ATP synthase subunit β Insulin resistance	Cytochrome C oxidase (COX) Forkhead box class-I (FoxO1) PGC-1α NADH dehydrogenase subunit IV (NADH) Protein kinase B (AKT)	Aging Cancer cachexia Disuse-induced muscle atrophy	[114,115]
Lymphatic system	Decreased ATP production Lower levels of mitochondrial respiratory chain complex enzymes	Adenylate kinase 2 (AK2) Tafazzin, Phospholipid-Lysophospholipid Transacylase (TAZ)	Severe combined immune deficiency disease (SCID)	[116]