Loss of mitochondrial DNA-encoded protein ND1 results in disruption of complex I biogenesis during early stages of assembly

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F16%3A10327250" target="_blank" >RIV/00216208:11110/16:10327250 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1096/fj.201500137R" target="_blank" >http://dx.doi.org/10.1096/fj.201500137R</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1096/fj.201500137R" target="_blank" >10.1096/fj.201500137R</a>

Result language

angličtina

Original language name

Loss of mitochondrial DNA-encoded protein ND1 results in disruption of complex I biogenesis during early stages of assembly

Original language description

Mitochondrial complex I (NADH:ubiquinone oxidoreductase) must be assembled precisely from 45 protein subunits for it to function correctly. One of its mitochondrial DNA (mtDNA) encoded subunits, ND1, is incorporated during the early stages of complex I assembly. However, little is known about how mutations in ND1 affect this assembly process. We found that in human 143B cybrid cells carrying a homoplasmic MT-ND1 mutation, ND1 protein could not be translated. As a result, the early stages of complex I assembly were disrupted, with mature complex I undetectable and complex I-linked respiration severely reduced to 2.0% of control levels. Interestingly, complex IV (ferrocytochrome c:oxygen oxidoreductase) steady-state levels were also reduced to 40.3%, possibly due to its diminished stability in the absence of respiratory supercomplex formation. This was in comparison with 143B cybrid controls (that contained wild-type mtDNA on the same nuclear background), which exhibited normal complex I, complex IV, and supercomplex assembly. We conclude that the loss of ND1 stalls complex I assembly during the early stages of its biogenesis, which not only results in the loss of mature complex I but also disrupts the stability of complex IV and the respiratory supercomplex to cause mitochondrial dysfunction.Lim, S. C., Hroudova, J., Van Bergen, N. J., Lopez Sanchez, M. I. G., Trounce, I. A., McKenzie, M. Loss of mitochondrial DNA-encoded protein ND1 results in disruption of complex I biogenesis during early stages of assembly.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

FASEB Journal

ISSN

0892-6638

e-ISSN

—

Volume of the periodical

30

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

2236-2248

UT code for WoS article

000376878300016

EID of the result in the Scopus database

2-s2.0-84973165770