The mammalian homologue of yeast Afg1 ATPase (lactation elevated 1) mediates degradation of nuclear-encoded complex IV subunits

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F16%3A00466466" target="_blank" >RIV/67985823:_____/16:00466466 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/16:10326296 RIV/00064165:_____/16:10326296

Result on the web

<a href="http://dx.doi.org/10.1042/BJ20151029" target="_blank" >http://dx.doi.org/10.1042/BJ20151029</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1042/BJ20151029" target="_blank" >10.1042/BJ20151029</a>

Result language

angličtina

Original language name

The mammalian homologue of yeast Afg1 ATPase (lactation elevated 1) mediates degradation of nuclear-encoded complex IV subunits

Original language description

Mitochondrial protein homeostasis is crucial for cellular function and integrity and is therefore maintained by several classes of proteins possessing chaperone and/or proteolytic activities. In the present study, we focused on characterization of LACE1 (lactation elevated 1) function in mitochondrial protein homeostasis. LACE1 is the human homologue of yeast mitochondrial Afg1 (ATPase family gene 1) ATPase, a member of the SEC18-NSF, PAS1, CDC48-VCP, TBP family. Yeast Afg1 was shown to mediate degradation of mitochondrially encoded complex IV subunits, and, on the basis of its similarity to CDC48 (p97/VCP), it was suggested to facilitate extraction of polytopic membrane proteins. We show that LACE1, which is a mitochondrial integral membrane protein, exists as part of three complexes of approximately 140, 400 and 500 kDa and is essential for maintenance of fused mitochondrial reticulum and lamellar cristae morphology. We demonstrate that LACE1 mediates degradation of nuclear-encoded complex IV subunits COX4 (cytochrome c oxidase 4), COX5A and COX6A, and is required for normal activity of complexes III and IV of the respiratory chain. Using affinity purification of LACE1–FLAG expressed in a LACE1-knockdown background, we show that the protein interacts physically with COX4 and COX5A subunits of complex IV and with mitochondrial inner-membrane protease YME1L. Finally, we demonstrate by ectopic expression of both K142A Walker A and E214Q Walker B mutants, that an intact ATPase domain is essential for LACE1-mediated degradation of nuclear-encoded complex IV subunits. Thus the present study establishes LACE1 as a novel factor with a crucial role in mitochondrial protein homeostasis.

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

<a href="/en/project/GA13-07223S" target="_blank" >GA13-07223S: Function of human ClpXP protease and LACE1 ATPase in mitochondrial biogenesis and protein homeostasis</a><br>

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

Biochemical Journal

ISSN

0264-6021

e-ISSN

—

Volume of the periodical

473

Issue of the periodical within the volume

6

Country of publishing house

GB - UNITED KINGDOM

Number of pages

8

Pages from-to

797-804

UT code for WoS article

000377208100013

EID of the result in the Scopus database

2-s2.0-84975144684