Mitochondrial complex I deficiency

The most common hereditary enzymatic defect of the OXIDATIVE PHOSPHORYLATION disorders that is linked to numerous diseases that can appear at any stage of life from birth through old age. These include MACROCEPHALY with progressive leukodystrophy, nonspecific encephalopathy, HYPERTROPHIC CARDIOMYOPATHY; MYOPATHY; LIVER DISEASES; LEIGH DISEASE; LEBER HEREDITARY OPTIC NEUROPATHY, and some cases of PARKINSON DISEASE. Mutations in both mitochondrial and nuclear genes for the components of NADH-ubiquinone reductase have been identified. OMIM: 252010

Also Known As:

Networked: 45 relevant articles (0 outcomes, 1 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Parkinson Disease (Parkinson's Disease)
2.	Leigh Disease (Leigh's Disease)
3.	Hypophosphatemic Rickets
4.	Hearing Loss (Hearing Impairment)
5.	Mitochondrial Diseases (Mitochondrial Disease)

Experts

1.	Smeitink, Jan A M: 4 articles (07/2022 - 04/2011)
2.	Schirris, Tom J J: 3 articles (07/2022 - 01/2021)
3.	Koopman, Werner J H: 3 articles (01/2022 - 04/2011)
4.	Willems, Peter H G M: 3 articles (01/2021 - 04/2011)
5.	Taylor, Robert W: 3 articles (01/2020 - 01/2016)
6.	Bénit, Paule: 3 articles (10/2019 - 09/2008)
7.	Rustin, Pierre: 3 articles (10/2019 - 09/2008)
8.	Frambach, Sanne J C M: 2 articles (07/2022 - 01/2021)
9.	Russel, Frans G M: 2 articles (07/2022 - 01/2021)
10.	de Haas, Ria: 2 articles (07/2022 - 01/2021)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Mitochondrial complex I deficiency:

1.	IronIBA 12/01/1992 - "Study of the substantia nigra after death in PD has highlighted three major changes: (1) evidence of oxidative stress and depletion of reduced glutathione; (2) high levels of total iron, with reduced ferritin buffering; and (3) mitochondrial complex I deficiency. "
2.	Glutathione (Reduced Glutathione)IBA 12/01/1992 - "Study of the substantia nigra after death in PD has highlighted three major changes: (1) evidence of oxidative stress and depletion of reduced glutathione; (2) high levels of total iron, with reduced ferritin buffering; and (3) mitochondrial complex I deficiency. "
3.	Ferritins (Ferritin)IBA 12/01/1992 - "Study of the substantia nigra after death in PD has highlighted three major changes: (1) evidence of oxidative stress and depletion of reduced glutathione; (2) high levels of total iron, with reduced ferritin buffering; and (3) mitochondrial complex I deficiency. "
4.	Proteins (Proteins, Gene)FDA Link 01/01/1989 - "Familial mitochondrial complex I deficiency with an abnormal mitochondrial encoded protein." 08/06/2013 - "Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure." 01/12/2015 - "Using Ndufs4 mouse model of mitochondrial complex I deficiency, we observed a remarkable ubiquitin protein increase in SN of Ndufs4-/- (KO) mice. " 09/15/2008 - "We showed previously that the Harlequin mouse phenotype was due to a specific mitochondrial complex I deficiency resulting from the loss of the Apoptosis Inducing Factor (Aif) protein. " 01/01/2017 - "Disorders of mitochondrial import, export and translation, including sideroblastic anemia with ataxia, EVEN-PLUS syndrome and mitochondrial complex I deficiency due to nucleotide-binding protein-like protein gene defect, have also been implicated in ISC biogenesis defects. "
5.	DNA (Deoxyribonucleic Acid)IBA 01/01/2016 - "We focus on pathologies due to mutations in nuclear DNA-encoded structural and assembly factors of the mitochondrial oxidative phosphorylation (OXPHOS) system, with a particular emphasis on isolated mitochondrial complex I deficiency. " 04/01/2011 - "Mouse models for nuclear DNA-encoded mitochondrial complex I deficiency." 06/01/2011 - "Cellular rescue-assay aids verification of causative DNA-variants in mitochondrial complex I deficiency." 07/01/1999 - "Nuclear DNA origin of mitochondrial complex I deficiency in fatal infantile lactic acidosis evidenced by transnuclear complementation of cultured fibroblasts." 01/01/2022 - "Mutations in the nuclear DNA-encoded NDUFS4 gene, encoding the NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) of complex I, induce 'mitochondrial complex I deficiency, nuclear type 1' (MC1DN1) and Leigh syndrome in paediatric patients. "
6.	Mitochondrial DNA (mtDNA)IBA 01/01/2020 - "Mitochondrial complex I deficiency is associated with a diverse range of clinical phenotypes and can arise due to either mitochondrial DNA (mtDNA) or nuclear gene defects. " 03/01/2016 - "Therefore, mitochondrial complex I deficiency and reduced mitochondrial DNA in the prefrontal cortex may be a hallmark of dementia in patients with PD." 01/01/2008 - "Mitochondrial complex I deficiency has been implicated in the pathogenesis of Parkinson's disease (PD), but as yet no mitochondrial DNA (mtDNA) variations have been identified that could account for the impaired complex I activity. "
7.	Apoptosis Inducing FactorIBA 01/01/2012 - "The Harlequin mutant mouse, characterized by loss of function of apoptosis-inducing factor, represents a reliable genetic model that resembles pathologies caused by human mitochondrial complex I deficiency. " 09/15/2008 - "We showed previously that the Harlequin mouse phenotype was due to a specific mitochondrial complex I deficiency resulting from the loss of the Apoptosis Inducing Factor (Aif) protein. "
8.	RotenoneIBA 04/01/2004 - "Skin fibroblasts from patients with mitochondrial complex I deficiency and normal fibroblasts during incubation with rotenone, or antimycin A, contained higher proportions of mitochondria in the swollen filamentous forms, nodal filaments, and ovoid forms rather than the slender filamentous forms in normal cells. " 12/01/1996 - "Values for NADH-cytochrome c reductase (rotenone sensitive) were compared for a series of three controls and nine patients with complex I (NADH-coenzyme Q reductase deficiency). "
9.	NucleotidesIBA 01/01/2021 - "The nucleotide binding protein-like (NUBPL) gene was first reported as a cause of mitochondrial complex I deficiency (MIM 613621, 618242) in 2010. " 01/01/2017 - "Disorders of mitochondrial import, export and translation, including sideroblastic anemia with ataxia, EVEN-PLUS syndrome and mitochondrial complex I deficiency due to nucleotide-binding protein-like protein gene defect, have also been implicated in ISC biogenesis defects. "
10.	NADH DehydrogenaseIBA 07/01/2023 - "Mutations in subunits of the mitochondrial NADH dehydrogenase cause mitochondrial complex I deficiency, a group of severe neurological diseases that can result in death in infancy. " 12/01/1996 - "Values for NADH-cytochrome c reductase (rotenone sensitive) were compared for a series of three controls and nine patients with complex I (NADH-coenzyme Q reductase deficiency). "

Therapies and Procedures

1.

Therapeutics 12/01/2001 - "The effect of agents commonly used in the therapy of mitochondrial complex I deficiency was examined in fibroblasts from a patient. " 01/01/2013 - "Successful Medical Therapy for Hypophosphatemic Rickets due to Mitochondrial Complex I Deficiency Induced de Toni-Debré-Fanconi Syndrome." 10/29/2019 - "Arabidopsis thaliana alternative dehydrogenases: a potential therapy for mitochondrial complex I deficiency? " 01/01/2021 - "Mitochondrial complex I deficiency in patients who have a nephrotic syndrome complaint may play a role in their responsiveness to steroid therapy and the development of SRNS and even the prognosis of their illness."