Mitochondrial stress response triggered by defects in protein synthesis quality control

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http://hdl.handle.net/10138/307109

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Richter , U , Ng , K Y , Suomi , F , Marttinen , P , Turunen , T , Jackson , C , Suomalainen , A , Vihinen , H , Jokitalo , E , Nyman , T A , Isokallio , M A , Stewart , J B , Mancini , C , Brusco , A , Seneca , S , Lombes , A , Taylor , R W & Battersby , B J 2019 , ' Mitochondrial stress response triggered by defects in protein synthesis quality control ' , Life Science Alliance , vol. 2 , no. 1 , 201800219 . https://doi.org/10.26508/lsa.201800219

Title: Mitochondrial stress response triggered by defects in protein synthesis quality control
Author: Richter, Uwe; Ng, Kah Ying; Suomi, Fumi; Marttinen, Paula; Turunen, Taina; Jackson, Christopher; Suomalainen, Anu; Vihinen, Helena; Jokitalo, Eija; Nyman, Tuula A.; Isokallio, Marita A.; Stewart, James B.; Mancini, Cecilia; Brusco, Alfredo; Seneca, Sara; Lombes, Anne; Taylor, Robert W.; Battersby, Brendan J.
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Research Programs Unit
University of Helsinki, HUSLAB
University of Helsinki, Institute of Biotechnology
University of Helsinki, University Management
University of Helsinki, Institute of Biotechnology
Date: 2019-02
Language: eng
Number of pages: 17
Belongs to series: Life Science Alliance
ISSN: 2575-1077
URI: http://hdl.handle.net/10138/307109
Abstract: Mitochondria have a compartmentalized gene expression system dedicated to the synthesis of membrane proteins essential for oxidative phosphorylation. Responsive quality control mechanisms are needed to ensure that aberrant protein synthesis does not disrupt mitochondrial function. Pathogenic mutations that impede the function of the mitochondrial matrix quality control protease complex composed of AFG3L2 and paraplegin cause a multifaceted clinical syndrome. At the cell and molecular level, defects to this quality control complex are defined by impairment to mitochondrial form and function. Here, we establish the etiology of these phenotypes. We show how disruptions to the quality control of mitochondrial protein synthesis trigger a sequential stress response characterized first by OMA1 activation followed by loss of mitochondrial ribosomes and by remodelling of mitochondrial inner membrane ultrastructure. Inhibiting mitochondrial protein synthesis with chloramphenicol completely blocks this stress response. Together, our data establish a mechanism linking major cell biological phenotypes of AFG3L2 pathogenesis and show how modulation of mitochondrial protein synthesis can exert a beneficial effect on organelle homeostasis.
Subject: M-AAA PROTEASE
COMPUTATIONAL PLATFORM
SPASTIC PARAPLEGIA
READ ALIGNMENT
DNA DELETIONS
MUTATIONS
OPA1
MEMBRANE
ATAXIA
TURNOVER
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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