NDLI: Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease

Content Provider	PubMed Central
Author	Davis, Robert E. Miller, Scott Herrnstadt, Corinna Ghosh, Soumitra S. Fahy, Eoin Shinobu, Leslie A. Douglas, Galasko Thal, Leon J. Beal, M. Flint Howell, Neil Parker, W. Davis
Copyright Year	1997
Abstract	Mounting evidence suggests that defects in energy metabolism contribute to the pathogenesis of Alzheimer disease (AD). Cytochrome c oxidase (CO) is kinetically abnormal, and its activity is decreased in brain and peripheral tissue in late-onset AD. CO is encoded by both the mitochondrial and the nuclear genomes. Its catalytic centers, however, are encoded exclusively by two mitochondrial genes, CO1 and CO2 (encoding CO subunits I and II, respectively). We searched these genes, as well as other mitochondrial genes, for mutations that might alter CO activity and cosegregate with AD. In the present study, specific missense mutations in the mitochondrial CO1 and CO2 genes but not the CO3 gene were found to segregate at a higher frequency with AD compared with other neurodegenerative or metabolic diseases. These mutations appear together in the same mitochondrial DNA molecule and define a unique mutant mitochondrial genome. Asymptomatic offspring of AD mothers had higher levels of these mutations than offspring of AD fathers, suggesting that these mutations can be maternally inherited. Cell lines expressing these mutant mitochondrial DNA molecules exhibited a specific decrease in CO activity and increased production of reactive oxygen species. We suggest that specific point mutations in the CO1 and CO2 genes cause the CO defect in AD. A CO defect may represent a primary etiologic event, directly participating in a cascade of events that results in AD.
Starting Page	4526
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	94
Language	English
Publisher	The National Academy of Sciences of the USA
Publisher Date	1997-04-29
Access Restriction	Open
Rights Holder	The National Academy of Sciences of the USA
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease

Novel Mitochondrial Transfer RNAPhe Gene Mutation Associated With Late-Onset Neuromuscular Disease

Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease

Modelling mitochondrial DNA mutations in bacterial cytochrome c oxidase: Link to colon cancer?

Mutations of the SCO1 Gene in Mitochondrial Cytochrome c Oxidase Deficiency with Neonatal-Onset Hepatic Failure and Encephalopathy

Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease

Oxidation of ferrocytochrome c by mitochondrial cytochrome c oxidase.

Mutations in APOPT1, Encoding a Mitochondrial Protein, Cause Cavitating Leukoencephalopathy with Cytochrome c Oxidase Deficiency

Crystallization of part of the mitochondrial electron transfer chain: cytochrome c oxidase--cytochrome c complex.

Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease

Similar Documents

Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease

Novel Mitochondrial Transfer RNAPhe Gene Mutation Associated With Late-Onset Neuromuscular Disease

Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease

Modelling mitochondrial DNA mutations in bacterial cytochrome c oxidase: Link to colon cancer?

Mutations of the SCO1 Gene in Mitochondrial Cytochrome c Oxidase Deficiency with Neonatal-Onset Hepatic Failure and Encephalopathy

Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease

Oxidation of ferrocytochrome c by mitochondrial cytochrome c oxidase.

Mutations in APOPT1, Encoding a Mitochondrial Protein, Cause Cavitating Leukoencephalopathy with Cytochrome c Oxidase Deficiency

Crystallization of part of the mitochondrial electron transfer chain: cytochrome c oxidase--cytochrome c complex.

Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease