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Organismal and Cellular Stress Responses upon Disruption of Mitochondrial Lonp1 Protease.
Taouktsi, Eirini; Kyriakou, Eleni; Smyrniotis, Stefanos; Borbolis, Fivos; Bondi, Labrina; Avgeris, Socratis; Trigazis, Efstathios; Rigas, Stamatis; Voutsinas, Gerassimos E; Syntichaki, Popi.
Affiliation
  • Taouktsi E; Laboratory of Molecular Genetics of Aging, Biomedical Research Foundation of the Academy of Athens, Center of Basic Research, 11527 Athens, Greece.
  • Kyriakou E; Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece.
  • Smyrniotis S; Laboratory of Molecular Genetics of Aging, Biomedical Research Foundation of the Academy of Athens, Center of Basic Research, 11527 Athens, Greece.
  • Borbolis F; Laboratory of Molecular Carcinogenesis and Rare Disease Genetics, Institute of Biosciences and Applications, National Center for Scientific Research "Demokritos", 15341 Athens, Greece.
  • Bondi L; Laboratory of Molecular Genetics of Aging, Biomedical Research Foundation of the Academy of Athens, Center of Basic Research, 11527 Athens, Greece.
  • Avgeris S; Laboratory of Molecular Genetics of Aging, Biomedical Research Foundation of the Academy of Athens, Center of Basic Research, 11527 Athens, Greece.
  • Trigazis E; Laboratory of Molecular Carcinogenesis and Rare Disease Genetics, Institute of Biosciences and Applications, National Center for Scientific Research "Demokritos", 15341 Athens, Greece.
  • Rigas S; Laboratory of Molecular Carcinogenesis and Rare Disease Genetics, Institute of Biosciences and Applications, National Center for Scientific Research "Demokritos", 15341 Athens, Greece.
  • Voutsinas GE; Laboratory of Molecular Genetics of Aging, Biomedical Research Foundation of the Academy of Athens, Center of Basic Research, 11527 Athens, Greece.
  • Syntichaki P; Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece.
Cells ; 11(8)2022 04 16.
Article de En | MEDLINE | ID: mdl-35456042
Cells engage complex surveillance mechanisms to maintain mitochondrial function and protein homeostasis. LonP1 protease is a key component of mitochondrial quality control and has been implicated in human malignancies and other pathological disorders. Here, we employed two experimental systems, the worm Caenorhabditis elegans and human cancer cells, to investigate and compare the effects of LONP-1/LonP1 deficiency at the molecular, cellular, and organismal levels. Deletion of the lonp-1 gene in worms disturbed mitochondrial function, provoked reactive oxygen species accumulation, and impaired normal processes, such as growth, behavior, and lifespan. The viability of lonp-1 mutants was dependent on the activity of the ATFS-1 transcription factor, and loss of LONP-1 evoked retrograde signaling that involved both the mitochondrial and cytoplasmic unfolded protein response (UPRmt and UPRcyt) pathways and ensuing diverse organismal stress responses. Exposure of worms to triterpenoid CDDO-Me, an inhibitor of human LonP1, stimulated only UPRcyt responses. In cancer cells, CDDO-Me induced key components of the integrated stress response (ISR), the UPRmt and UPRcyt pathways, and the redox machinery. However, genetic knockdown of LonP1 revealed a genotype-specific cellular response and induced apoptosis similar to CDDO-Me treatment. Overall, the mitochondrial dysfunction ensued by disruption of LonP1 elicits adaptive cytoprotective mechanisms that can inhibit cancer cell survival but diversely modulate organismal stress response and aging.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Peptide hydrolases / Protéines de Caenorhabditis elegans Limites: Animals Langue: En Journal: Cells Année: 2022 Type de document: Article Pays d'affiliation: Grèce Pays de publication: Suisse

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Peptide hydrolases / Protéines de Caenorhabditis elegans Limites: Animals Langue: En Journal: Cells Année: 2022 Type de document: Article Pays d'affiliation: Grèce Pays de publication: Suisse