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Novel roles of RTN4 and CLIMP-63 in regulating mitochondrial structure, bioenergetics and apoptosis.
Carter, Rachel J; Milani, Mateus; Beckett, Alison J; Liu, Shiyu; Prior, Ian A; Cohen, Gerald M; Varadarajan, Shankar.
Afiliação
  • Carter RJ; Departments of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3GE, UK.
  • Milani M; Departments of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3GE, UK.
  • Beckett AJ; Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3GE, UK.
  • Liu S; Departments of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3GE, UK.
  • Prior IA; Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3GE, UK.
  • Cohen GM; Departments of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3GE, UK.
  • Varadarajan S; Departments of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3GE, UK. svar@liverpool.ac.uk.
Cell Death Dis ; 13(5): 436, 2022 05 04.
Article em En | MEDLINE | ID: mdl-35508606
ABSTRACT
The recruitment of DRP1 to mitochondrial membranes prior to fission is facilitated by the wrapping of endoplasmic reticulum (ER) membranes around the mitochondria. To investigate the complex interplay between the ER membranes and DRP1 in the context of mitochondrial structure and function, we downregulate two key ER shaping proteins, RTN4 and CLIMP-63, and demonstrate pronounced mitochondrial hyperfusion and reduced ER-mitochondria contacts, despite their differential regulation of ER architecture. Although mitochondrial recruitment of DRP1 is unaltered in cells lacking RTN4 or CLIMP-63, several aspects of mitochondrial function, such as mtDNA-encoded translation, respiratory capacity and apoptosis are significantly hampered. Further mechanistic studies reveal that CLIMP-63 is required for cristae remodeling (OPA1 proteolysis) and DRP1-mediated mitochondrial fission, whereas both RTN4 and CLIMP-63 regulate the recruitment of BAX to ER and mitochondrial membranes to enable cytochrome c release and apoptosis, thereby performing novel and distinct roles in the regulation of mitochondrial structure and function.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dinaminas / Mitocôndrias Idioma: En Revista: Cell Death Dis Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dinaminas / Mitocôndrias Idioma: En Revista: Cell Death Dis Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Reino Unido