Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones.
Protein folding in the mitochondria is assisted by nuclear-encoded compartment-specific chaperones but regulation of the expression of their encoding genes is poorly understood. We found that the mitochondrial matrix HSP70 and HSP60 chaperones, encoded by the Caenorhabditis elegans hsp-6 and hsp-60 genes, were selectively activated by perturbations that impair assembly of multi-subunit mitochondrial complexes or by RNAi of genes encoding mitochondrial chaperones or proteases, which lead to defective protein folding and processing in the organelle. hsp-6 and hsp-60 induction was specific to perturbed mitochondrial protein handling, as neither heat-shock nor endoplasmic reticulum stress nor manipulations that impair mitochondrial steps in intermediary metabolism or ATP synthesis activated the mitochondrial chaperone genes. These observations support the existence of a mitochondrial unfolded protein response that couples mitochondrial chaperone gene expression to changes in the protein handling environment in the organelle.
Yoneda
Takunari
T
Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
Benedetti
Cristina
C
Urano
Fumihiko
F
Clark
Scott G
SG
Harding
Heather P
HP
Ron
David
D
D000818:Animals; D017173:Caenorhabditis elegans; D002451:Cell Compartmentation / Q000502:physiology*; D018834:Chaperonin 60 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D046911:Macromolecular Substances / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D017510:Protein Folding; D034622:RNA Interference; D015533:Transcriptional Activation / Q000502:physiology
D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D046911:Macromolecular Substances; D018832:Molecular Chaperones