bims-mitlys Biomed News
on Mitochondria and Lysosomes
Issue of 2021–09–05
four papers selected by
Nicoletta Plotegher, University of Padova
  1. Vps13D functions in a Pink1-dependent and Parkin-independent mitophagy pathway.
  2. APOE4 expression is associated with impaired autophagy and mitophagy in astrocytes.
  3. Role of mitochondrial dysfunction and PINK1/Parkin-mediated mitophagy in Cd-induced hepatic lipid accumulation in chicken embryos.
  4. Organelle-specific regulation of ferroptosis.
  1. J Cell Biol. 2021 Nov 01. pii: e202104073. [Epub ahead of print]220(11):
    Vps13D functions in a Pink1-dependent and Parkin-independent mitophagy pathway.
    James L Shen, Tina M Fortier, Ruoxi Wang, Eric H Baehrecke.
      Defects in autophagy cause problems in metabolism, development, and disease. The autophagic clearance of mitochondria, mitophagy, is impaired by the loss of Vps13D. Here, we discover that Vps13D regulates mitophagy in a pathway that depends on the core autophagy machinery by regulating Atg8a and ubiquitin localization. This process is Pink1 dependent, with loss of pink1 having similar autophagy and mitochondrial defects as loss of vps13d. The role of Pink1 has largely been studied in tandem with Park/Parkin, an E3 ubiquitin ligase that is widely considered to be crucial in Pink1-dependent mitophagy. Surprisingly, we find that loss of park does not exhibit the same autophagy and mitochondrial deficiencies as vps13d and pink1 mutant cells and contributes to mitochondrial clearance through a pathway that is parallel to vps13d. These findings provide a Park-independent pathway for Pink1-regulated mitophagy and help to explain how Vps13D regulates autophagy and mitochondrial morphology and contributes to neurodegenerative diseases.
    DOI:  https://doi.org/10.1083/jcb.202104073
  2. Neural Regen Res. 2022 Apr;17(4): 777-778
    APOE4 expression is associated with impaired autophagy and mitophagy in astrocytes.
    Schmukler Eran, Pinkas-Kramarski Ronit.
      
    DOI:  https://doi.org/10.4103/1673-5374.322452
  3. Life Sci. 2021 Aug 31. pii: S0024-3205(21)00893-6. [Epub ahead of print] 119906
    Role of mitochondrial dysfunction and PINK1/Parkin-mediated mitophagy in Cd-induced hepatic lipid accumulation in chicken embryos.
    Dawei Chen, Di Ran, Chao Wang, Yinyin Liu, Yonggang Ma, Ruilong Song, Yushi Gao, Zongping Liu.
      The present study was performed to investigate the effects of Cd exposure on lipid metabolism and mitochondrial dysfunction and to explore the role of mitophagy in Cd-induced dysregulation of lipid metabolism in chicken embryo liver tissues and hepatocytes. To this end, seven-day-old chicken embryos were exposed to different concentrations of Cd for 7 days, and primary chicken embryo hepatocytes were treated with Cd at four different concentrations for 6 h. Furthermore, the mitophagy inhibitor cyclosporine A (CsA) was used to investigate the role of mitophagy in Cd-induced disruption of lipid metabolism. Lipid accumulation, the expression levels of genes involved in lipid metabolism, mitochondrial dysfunction, and mitophagy were measured. The results demonstrated that Cd exposure increases hepatic triglyceride (TG) accumulation and the expression levels of lipogenic genes while decreasing those of lipolytic genes. Furthermore, Cd exposure was observed to alter mitochondrial morphology in terms of reduced size, excessive mitochondrial damage, and the formation of mitophagosomes. The co-localization of lysosome-associated membrane glycoprotein 2 and LC3 puncta was significantly increased in primary chicken embryo hepatocytes after Cd exposure. Moreover, Cd exposure increased LC3, PINK1, and Parkin protein expression levels. CsA effectively alleviated Cd-induced mitochondrial dysfunction, blocked mitochondrial membrane potential collapse, and suppressed PINK1/Parkin-mediated mitophagy. Furthermore, CsA treatment reversed the Cd-induced TG accumulation in liver tissues but further increased it in hepatocytes. Taken together, our findings demonstrate (for the first time) the importance of mitochondrial dysfunction and mitophagy via the PINK1/Parkin pathway in Cd-induced disruption of lipid metabolism.
    Keywords:  Cadmium; Chicken; Hepatocyte; Lipid metabolism; Liver; Mitophagy; PINK1/Parkin
    DOI:  https://doi.org/10.1016/j.lfs.2021.119906
  4. Cell Death Differ. 2021 Aug 31.
    Organelle-specific regulation of ferroptosis.
    Xin Chen, Rui Kang, Guido Kroemer, Daolin Tang.
      Ferroptosis, a cell death modality characterized by iron-dependent lipid peroxidation, is involved in the development of multiple pathological conditions, including ischemic tissue damage, infection, neurodegeneration, and cancer. The cellular machinery responsible for the execution of ferroptosis integrates multiple pro-survival or pro-death signals from subcellular organelles and then 'decides' whether to engage the lethal process or not. Here, we outline the evidence implicating different organelles (including mitochondria, lysosomes, endoplasmic reticulum, lipid droplets, peroxisomes, Golgi apparatus, and nucleus) in the ignition or avoidance of ferroptosis, while emphasizing their potential relevance for human disease and their targetability for pharmacological interventions.
    DOI:  https://doi.org/10.1038/s41418-021-00859-z
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