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.
Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
Takunari
T
Yoneda
Cristina
C
Benedetti
Fumihiko
F
Urano
Scott G
SG
Clark
Heather P
HP
Harding
David
D
Ron
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