Mitochondrial Respiratory Deficiencies Signal Up-regulation of Genes for Heat Shock Proteins

Abstract

The consequences of mitochondrial dysfunction are not limited to the development of oxidative stress or initiation of apoptosis but can result in the establishment of stress tolerance. Using maize mitochondrial mutants, we show that permanent mitochondrial deficiencies trigger novel Ca 2؉ -independent signaling pathways, leading to constitutive expression of genes for molecular chaperones, heat shock proteins (HSPs) of different classes. The signaling to activate hsp genes appears to originate from a reduced mitochondrial transmembrane potential. Upon depolarization of mitochondrial membranes in transient assays, gene induction for mitochondrial HSPs occurred more rapidly than that for cytosolic HSPs. We also demonstrate that in the nematode Caenorhabditis elegans transcription of hsp genes can be induced by RNA interference of nuclear respiratory genes. In both organisms, activation of hsp genes in response to mitochondrial impairment is distinct from their responses to heat shock and is not associated with oxidative stress. Thus, mitochondria-to-nucleus signaling to express a hsp gene network is apparently a widespread retrograde mechanism to facilitate cell defense and survival.

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

“…Increased expression of hsp-16 is linked to daf-16 activation (Walker and Lithgow, 2003). Stimulation of hsp-16 expression may also result from reduced membrane potential of mitochondria (Kuzmin et al, 2004). In normal worms, hsp-16 is expressed ubiquitously in somatic tissues and is likely to function as a passive ligand, temporarily preventing unfolded proteins from aggregating.…”

The Pentatricopeptide Repeat Protein OTP87 Is Essential for RNA Editing of nad7 and atp1 Transcripts in Arabidopsis Mitochondria

“…Additional immunodetection shows that the Hsp70 chaperone is overexpressed in otp87 compared with the wild type. This overexpression may reflect a mitochondrial dysfunction in otp87 as previous studies reported the activation of hsp genes in response to mitochondrial impairment (49).…”

Mitochondrial Reactive Oxygen Species. Contribution to Oxidative Stress and Interorganellar Signaling

“…In addition to sharing downstream, PCD-related mitochondrial events, inhibition of the mtETC by chemicals or by mutation and inhibition by pathogen challenge share similar gene induction profiles, evidence of similar MRR signaling occurring in each of these cases. Nuclear genes induced by harpin overlap with nuclear genes induced by disruption of the mtETC by mitochondrial mutants (Karpova et al, 2002;Krause and Durner, 2004;Kuzmin et al, 2004). In addition, the profile of the whole transcriptome response to AA is most similar to the transcriptome responses to pathogen attack (Yu et al, 2001 (Subbaiah et al, 1998, and refs.…”

“…Altered nuclear gene expression is part of this new homeostasis. Mutants exhibit altered expression of genes encoding AOXs, heat shock proteins, and antioxidant enzymes (Karpova et al, 2002;Dutilleul et al, 2003;Kuzmin et al, 2004). Thus, permanent alteration of mtETC function results in constitutively altered nuclear gene expression.…”

“…In addition, the profile of the whole transcriptome response to AA is most similar to the transcriptome responses to pathogen attack (Yu et al, 2001 (Subbaiah et al, 1998, and refs. therein;Tsuji et al, 2000;Kuzmin et al, 2004). Modulation of mtROS levels by AOX is likely to be an important early step preceding the above sequence of events.…”