Chaperonin—Co-chaperonin Interactions - The Networking of Chaperones by Co-chaperones - page 164

any other known Cpn10 protein that is not essential for function, but plays a role in
preventing aggregation at high temperatures (Luke et al. 2005 ; Chen et al. 2008 ).
Roles of Eukaryotic Group I Chaperonins
In eukaryotes, Hsp60 is found in the cytosol and the mitochondria and also in chlo-
roplasts of plants. It interacts with its co-chaperonin Hsp10 or Cpn10 to promote
protein folding in the cell. Most mitochondria and chloroplasts in higher plants ap-
pear to possess multiple chaperonin subunits (Hill and Hemmingsen 2001 ). Chap-
eronins in the eukaryotic cytosol are frequently situated near the ribosome and are
found in complexes with other chaperones such as Hsc70 (Thulasiraman et al. 1999 ).
In recent years a number of novel functions and interacting molecules have been
assigned to Hsp60 (Czarnecka et al. 2006 ). Some of these are associated with car-
cinogenesis as its role in the survival and proliferation of tumor cells has increased
(Czarnecka et al. 2006 ; Cappello et al. 2008 ).
The mitochondrial Hsp60 protein is essential for the folding of proteins imported
into the mitochondria and prevention of denaturation during stress (Cheng et al.
1989 ; Levy-Rimler et al. 2001 ). They are also characterised by a host of additional
functions, including extracellular functions. Mutations of human Hsp60 are linked
to severe genetic diseases (Bross et al. 2007 ; Hansen et al. 2007 ; Magen et al. 2008 ).
It also plays a role in the production of pro-inflammatory cytokines (Chun et al.
2010). In addition, it plays both pro-apoptotic and anti-apoptotic roles, depending
on localisation (Xanthoudakis et al. 1999 ; Knowlton and Gupta 2003 ). The mito-
chondrial Hsp60 in eukaryotic cells is composed of a double-ring structure capped
by one ring of Hsp10 (Azem et al. 1995 ; Coluzza et al. 2006 ). In contrast, human
Hsp60 exists basically in a single-ring to double-ring equilibrium and Hsp10 can
bind to both single and double-ring Hsp60 in the presence of ATP (Azem et al.
1995 ). The mitochondrial chaperonin complex that is composed of a single ring of
seven subunits and a ring of Hsp10 subunits cannot exploit binding of ATP to the
trans ring as a mechanism for releasing cis GroES (Nielsen and Cowan 1998 ). This
complex may have evolved an intrinsically lower affinity for the co-chaperonin but
the presence of a high affinity mobile loop on Hsp10 may offset the low affinity
(Nielsen and Cowan 1998 ). Despite the fact that mitochondrial Hsp60 can function-
ally replace GroEL, it is incapable of interacting with GroES (Nielsen et al. 1999 ).
The elements that dictate the specificity of mitochondrial Hsp60 for Hsp10 appear
to lie in the apical domain (Parnas et al. 2012 ). Analysis of in vivo substrates of
yeast mitochondrial chaperonins revealed divergent chaperonin requirements, indi-
cating that Hsp60 and Hsp10 do not always operate as a functional unit (Dubaquie
et al. 1998 ). Yeast mitochondrial Hsp60 can bind to single-stranded DNA in vitro
and play a role in the structure and transmission of nucleoids (Kaufman et al. 2003 ).
A number of parasites affecting human health have demonstrated an up-regulation
of Hsp60, which is possibly linked to diverse environmental conditions encountered