Editing GroEL (section)

== Function ==

=== Common ===
Heat shock proteins are amongst the most [[Protein family|evolutionarily conserved of proteins]].<ref name=five/> The significant function, structural, and sequential homology between HSP60 and its prokaryotic homolog, groEL, demonstrates this level of conservation. Moreover, HSP60’s amino acid sequence bears a similarity to its homolog in [[plants]], [[bacteria]], and [[humans]].<ref name=seven>{{cite journal  |vauthors=Johnson RB, etal |title=Cloning and characterization of the yeast chaperonin HSP60 gene |journal=Genetics |volume=84 |issue=2 |pages=295–300 |year=2003 |doi=10.1016/0378-1119(89)90503-9 |pmid=2575559}}</ref> Heat shock proteins are primarily responsible for maintaining the integrity of cellular proteins particularly in response to environmental changes. Stresses such as temperature, concentration imbalance, pH change, and toxins can all induce heat shock proteins to maintain the conformation of the cell’s proteins. HSP60 aids in the folding and conformation maintenance of approximately 15-30% of all cellular proteins.<ref name=six/> In addition to HSP60’s typical role as a heat shock protein, studies have shown that HSP60 plays an important role in the [[transport]] and maintenance of mitochondrial proteins as well as the [[Transmission (genetics)|transmission]] and [[DNA replication|replication]] of mitochondrial [[DNA]].

=== Mitochondrial protein transport ===
HSP60 possesses two main responsibilities with respect to mitochondrial protein transport. It functions to [[catalyze]] the folding of proteins destined for the matrix and maintains protein in an unfolded state for transport across the inner membrane of the mitochondria.<ref name=eight>{{cite journal  |vauthors=Koll H, etal |title=Antifolding activity of hsp60 couples protein import into the mitochondrial matrix with export to the intermembrane space |journal=Cell |volume=68 |issue=6 |pages=1163–75 |date=March 1992 |pmid=1347713 |url=https://epub.ub.uni-muenchen.de/7621/1/Neupert_Walter_7621.pdf|doi=10.1016/0092-8674(92)90086-R|s2cid=7430067 }}</ref> Many proteins are targeted for processing in the matrix of the mitochondria but then are quickly exported to other parts of the cell. The hydrophobic portion HSP60 is responsible for maintaining the unfolded conformation of the protein for transmembrane transport.<ref name=eight/> Studies have shown how HSP60 binds to incoming proteins and induces conformational and structural changes. Subsequent changes in ATP concentrations hydrolyze the bonds between the protein and HSP60 which signals the protein to exit the mitochondria.<ref name=eight/> HSP60 is also capable of distinguishing between proteins designated for export and proteins destined to remain in the mitochondrial matrix by looking for an [[amphiphilic]] alpha-helix of 15-20 residues.<ref name=eight/> The existence of this sequence signals that the protein is to be exported while the absence signals that the protein is to remain in the mitochondria. The precise mechanism is not yet entirely understood.

=== DNA metabolism ===
In addition to its critical role in protein folding, HSP60 is involved in the replication and transmission of [[mitochondrial DNA]]. In extensive studies of HSP60 activity in ''Saccharomyces cerevisiae'', scientists have proposed that HSP60 binds preferentially to the single stranded [[template DNA]] strand in a tetradecamer like complex <ref name=ten>Kaufman, BA. Studies on mitochondria DNA nucleoids in Saccharomyces cerevisiae: identification of bifunctional proteins. ''In Genetics and Development'', UT Southwestern Medical Center at Dallas, Dallas, TX. 241pp.</ref>
This tetradecamer complex interacts with other transcriptional elements to serve as a regulatory mechanism for the replication and transmission of mitochondrial DNA. Mutagenic studies have further supported HSP60 regulatory involvement in the replication and transmission of mitochondrial DNA.<ref name="Kaufman2003">{{cite journal|last1=Kaufman|first1=B. A.|title=A function for the mitochondrial chaperonin Hsp60 in the structure and transmission of mitochondrial DNA nucleoids in Saccharomyces cerevisiae|journal=The Journal of Cell Biology|volume=163|issue=3|year=2003|pages=457–461|issn=0021-9525|doi=10.1083/jcb.200306132|pmid=14597775|pmc=2173642}}</ref>[[Mutations]] in HSP60 increase the levels of mitochondrial DNA and result in subsequent transmission defects.

=== Cytoplasmic vs mitochondrial HSP60 ===
In addition to the already illustrated structural differences between cytoplasmic and mitochondrial HSP60, there are marked functional differences. Studies have suggested that HSP60 plays a key role in preventing [[apoptosis]] in the cytoplasm. The cytoplasmic HSP60 forms a complex with proteins responsible for apoptosis and regulates the activity of these proteins.<ref name=one/> The cytoplasmic version is also involved in [[immune]] response and [[cancer]].<ref name=one/>  These two aspects will be elaborated on later. Extremely recent investigations have begun to suggest a regulatory correlation between HSP60 and the [[glycolysis|glycolytic]] enzyme, 6-[[phosphofructokinase-1]]. Although not much information is available, cytoplasmic HSP60 concentrations have influenced the expression of 6-phosphofructokinase in [[glycolysis]].<ref name=eleven>{{cite journal  |vauthors=Koll H, etal |title=Antifolding Activity of HSP60 Couples Protein Import into the Mitochondrial Matrix with Export to the Intermembrane Space |journal=Cell |volume=68 |pages=1163–75 |year=1992 |doi=10.1016/0092-8674(92)90086-R |pmid=1347713 |issue=6|s2cid=7430067 |url=https://epub.ub.uni-muenchen.de/7621/1/Neupert_Walter_7621.pdf }}</ref> Despite these marked differences between the cytoplasmic and mitochondrial form, experimental analysis has shown that the cell is quickly capable of moving cytoplasmic HSP60 into the mitochondria if environmental conditions demand a higher presence of mitochondrial HSP60.<ref name=one/>