HSP78 encodes a yeast mitochondrial heat shock protein in the Clp family of ATP-dependent proteases.

Abstract

The Saccharomyces cerevisiae nuclear gene for a 78-kDa mitochondrial heat shock protein (hsp78) was identified in a Agtll expression library through immunological screening with an hsp78-specific monoclonal antibody. Cells exposed to physiological stress, such as an abrupt elevation in temperature, synthesize a subset of highly conserved cellular proteins collectively known as the heat shock or stress proteins. Many members of the heat shock protein (HSP) families are expressed in the absence of stress and function as molecular chaperones in the folding of newly synthesized polypeptide chains and in the assembly of oligomeric structures (for recent reviews, see references 2 and 13). Heat shock proteins also appear to be involved in the degradation of unfolded or damaged polypeptides, either by catalyzing proteolysis or by presenting polypeptides to the active proteases. Well-known examples of heat-shockinducible proteins involved in protein degradation are ubiquitin in eukaryotes (55) and the ATP-dependent La (Lon) and ClpP proteases in prokaryotes (4,30). In addition, members of the newly discovered family of Clp proteins appear to combine an involvement in proteolysis with many of the characteristics of molecular chaperones, i.e., several are heat shock proteins, they are highly conserved in both prokaryotes and eukaryotes, and in eukaryotes, multiple forms or subfamilies appear to be partitioned in different cellular compartments.The wide distribution of the Clp family of proteins became apparent when the sequence of the ClpA subunit of the two-component ClpA-ClpP ATP-dependent protease (18), also known as the Ti protease (21), was found to be related to a number of previously described proteins with known sequences but unknown functions. These proteins, now * Corresponding author. t Present address:

A soybean 101-kD heat shock protein complements a yeast HSP104 deletion mutant in acquiring thermotolerance.

“…Like other Hsp gene families, the Clp gene family includes members that are induced by heat stress and members that are constitutively expressed. Heat-inducible Clp proteins characterized to date are members of the ClpB subfamily (Sanchez and Lindquist, 1990;Kitagawa et al, 1991;Squires et al, 1991;Squires and Squires, 1992;Leonhardt et al, 1993). The accumulation of the transcripts that hybridized to the GmHsplOl cDNA was strictly heat inducible, as shown by RNA gel blot hybridization analyses (Figure 3).…”

The ClpB Homolog Hsp78 Is Required for the Efficient Degradation of Proteins in the Mitochondrial Matrix

“…Bacteria contain various subtypes of the Clp/Hsp100 chaperone proteins, whereas only three family members have been identified in Saccharomyces cerevisiae. Hsp104, which is located in the cytosol (4), and Hsp78, found in the mitochondrial matrix (5), are homologs of the bacterial ClpB and therefore belong to a subtype that shows no direct association with the ClpP protease (6). ClpB has recently been shown to be involved in the reactivation of aggregated proteins in cooperation with the Hsp70 system in E. coli (7)(8)(9).…”

T7 RNA polymerase-dependent expression of COXII in yeast mitochondria.

“…Overall mitochondrial transcription is repressed in cells growing fermentatively on glucose but increases three-to sixfold when cells are grown under respiratory conditions (38,63). This modest derepression of mitochondrial transcription differs dramatically from the expression of nuclear genes for mitochondrial proteins, many of which are induced from 10-to 100-fold at the transcriptional level in response not only to carbon source but also to several other variables, including heme (24), heat shock (34), and even mitochondrial genotype (48).…”