PT  - JOURNAL ARTICLE
AU  - Uwe Richter
AU  - Kah Ying Ng
AU  - Fumi Suomi
AU  - Paula Marttinen
AU  - Taina Turunen
AU  - Christopher Jackson
AU  - Anu Suomalainen
AU  - Helena Vihinen
AU  - Eija Jokitalo
AU  - Tuula A Nyman
AU  - Marita A Isokallio
AU  - James B Stewart
AU  - Cecilia Mancini
AU  - Alfredo Brusco
AU  - Sara Seneca
AU  - Anne Lombès
AU  - Robert W Taylor
AU  - Brendan J Battersby
TI  - Mitochondrial stress response triggered by defects in protein synthesis quality control
AID  - 10.26508/lsa.201800219
DP  - 2019 Feb 01
TA  - Life Science Alliance
PG  - e201800219
VI  - 2
IP  - 1
4099  - https://www.life-science-alliance.org/content/2/1/e201800219.short
4100  - https://www.life-science-alliance.org/content/2/1/e201800219.full
SO  - Life Sci. Alliance2019 Feb 01; 2
AB  - 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.