scholarly journals Cyclophilin 20 is involved in mitochondrial protein folding in cooperation with molecular chaperones Hsp70 and Hsp60.

1995 ◽  
Vol 15 (5) ◽  
pp. 2654-2662 ◽  
Author(s):  
J Rassow ◽  
K Mohrs ◽  
S Koidl ◽  
I B Barthelmess ◽  
N Pfanner ◽  
...  
Keyword(s):  
Protein Folding ◽  
Cyclosporin A ◽  
Molecular Chaperones ◽  
Mitochondrial Protein ◽  
The Matrix ◽  
Inhibitory Drug ◽  
Preprotein Translocation ◽  
Cellular Compartments ◽  
Precursor Molecules

We studied the role of mitochondrial cyclophilin 20 (CyP20), a peptidyl-prolyl cis-trans isomerase, in preprotein translocation across the mitochondrial membranes and protein folding inside the organelle. The inhibitory drug cyclosporin A did not impair membrane translocation of preproteins, but it delayed the folding of an imported protein in wild-type mitochondria. Similarly, Neurospora crassa mitochondria lacking CyP20 efficiently imported preproteins into the matrix, but folding of an imported protein was significantly delayed, indicating that CyP20 is involved in protein folding in the matrix. The slow folding in the mutant mitochondria was not inhibited by cyclosporin A. Folding intermediates of precursor molecules reversibly accumulated at the molecular chaperones Hsp70 and Hsp60 in the matrix. We conclude that CyP20 is a component of the mitochondrial protein folding machinery and that it cooperates with Hsp70 and Hsp60. It is speculated that peptidyl-prolyl cis-trans isomerases in other cellular compartments may similarly promote protein folding in cooperation with chaperone proteins.

scholarly journals Role of the chaperonin cofactor Hsp10 in protein folding and sorting in yeast mitochondria.

1994 ◽  
Vol 126 (2) ◽  
pp. 305-315 ◽  
Author(s):  
J Höhfeld ◽  
F U Hartl
Keyword(s):  
Protein Folding ◽  
Mitochondrial Protein ◽  
Temperature Sensitive ◽  
Intermembrane Space ◽  
Permissive Temperature ◽  
Loop Region ◽  
The Matrix

Protein folding in mitochondria is mediated by the chaperonin Hsp60, the homologue of E. coli GroEL. Mitochondria also contain a homologue of the cochaperonin GroES, called Hsp10, which is a functional regulator of the chaperonin. To define the in vivo role of the co-chaperonin, we have used the genetic and biochemical potential of the yeast S. cerevisiae. The HSP10 gene was cloned and sequenced and temperature-sensitive lethal hsp10 mutants were generated. Our results identify Hsp10 as an essential component of the mitochondrial protein folding apparatus, participating in various aspects of Hsp60 function. Hsp10 is required for the folding and assembly of proteins imported into the matrix compartment, and is involved in the sorting of certain proteins, such as the Rieske Fe/S protein, passing through the matrix en route to the intermembrane space. The folding of the precursor of cytosolic dihydrofolate reductase (DHFR), imported into mitochondria as a fusion protein, is apparently independent of Hsp10 function consistent with observations made for the chaperonin-mediated folding of DHFR in vitro. The temperature-sensitive mutations in Hsp10 map to a domain (residues 25-40) that corresponds to a previously identified mobile loop region of bacterial GroES and result in a reduced binding affinity of hsp10 for the chaperonin at the non-permissive temperature.

scholarly journals Teasing Apart the Role of the Ribosome and Molecular Chaperones in Cellular Protein Folding

2018 ◽  
Vol 114 (3) ◽  
pp. 414a
Author(s):  
Rayna M. Addabbo ◽  
Matthew D. Dalphin ◽  
Yue Liu ◽  
Miranda F. Mecha ◽  
Silvia Cavagnero
Keyword(s):  
Protein Folding ◽  
Molecular Chaperones ◽  
Cellular Protein

Role of Molecular Chaperones in Protein Folding

2010 ◽  
pp. 47-72 ◽  
Author(s):  
Kausik Chakraborty ◽  
Florian Georgescauld ◽  
Manajit Hayer-Hartl ◽  
F. Ulrich Hartl
Keyword(s):  
Protein Folding ◽  
Molecular Chaperones

scholarly journals Mitochondrial assembly: protein import

2004 ◽  
Vol 63 (2) ◽  
pp. 293-300 ◽  
Author(s):  
David A. Hood ◽  
Anna-Maria Joseph
Keyword(s):  
Molecular Chaperones ◽  
Mammalian Cells ◽  
Protein Import ◽  
Contractile Activity ◽  
Mitochondrial Protein ◽  
Energy Status ◽  
Mitochondrial Protein Import ◽  
Physiological Importance ◽  
The Matrix ◽  
Import Receptors

The protein import process of mitochondria is vital for the assembly of the hundreds of nuclear-derived proteins into an expanding organelle reticulum. Most of our knowledge of this complex multisubunit network comes from studies of yeast and fungal systems, with little information known about the protein import process in mammalian cells, particularly skeletal muscle. However, growing evidence indicates that the protein import machinery can respond to changes in the energy status of the cell. In particular, contractile activity, a powerful inducer of mitochondrial biogenesis, has been shown to alter the stoichiometry of the protein import apparatus via changes in several protein import machinery components. These adaptations include the induction of cytosolic molecular chaperones that transport precursors to the matrix, the up-regulation of outer membrane import receptors, and the increase in matrix chaperonins that facilitate the import and proper folding of the protein for subsequent compartmentation in the matrix or inner membrane. The physiological importance of these changes is an increased capacity for import into the organelle at any given precursor concentration. Defects in the protein import machinery components have been associated with mitochondrial disorders. Thus, contractile activity may serve as a possible mechanism for up-regulation of mitochondrial protein import and compensation for mitochondrial phenotype alterations observed in diseased muscle.

The role of molecular chaperones in protein folding.

1995 ◽  
Vol 9 (15) ◽  
pp. 1559-1569 ◽  
Author(s):  
J P Hendrick ◽  
F U Hartl
Keyword(s):  
Protein Folding ◽  
Molecular Chaperones

scholarly journals A Nonconventional Role of Molecular Chaperones: Involvement in the Cytoarchitecture

Physiology ◽  
2001 ◽  
Vol 16 (3) ◽  
pp. 123-126 ◽  
Author(s):  
Peter Csermely
Keyword(s):  
Protein Folding ◽  
Molecular Chaperones ◽  
Eukaryotic Cells ◽  
Intracellular Traffic

A hallmark of chaperone action is assistance in protein folding. Indeed, folding of nascent prokaryotic proteins proceeds mostly as a chaperone-assisted, posttranslational event. On the contrary, in nonstressed eukaryotic cells folding-related tasks of eukaryotic chaperones are restricted to a subset of proteins, and “jobless” chaperones may form an extension of the cytoarchitecture, facilitating intracellular traffic of proteins and other macromolecules.

scholarly journals Pam17 Is Required for Architecture and Translocation Activity of the Mitochondrial Protein Import Motor

2005 ◽  
Vol 25 (17) ◽  
pp. 7449-7458 ◽  
Author(s):  
Martin van der Laan ◽  
Agnieszka Chacinska ◽  
Maria Lind ◽  
Inge Perschil ◽  
Albert Sickmann ◽  
...  
Keyword(s):  
Protein Import ◽  
Mitochondrial Protein ◽  
Matrix Proteins ◽  
Stable Complex ◽  
Nucleotide Exchange ◽  
Inner Membrane ◽  
Reading Frame ◽  
Nucleotide Exchange Factor ◽  
The Matrix ◽  
Preprotein Translocation

ABSTRACT Import of mitochondrial matrix proteins involves the general translocase of the outer membrane and the presequence translocase of the inner membrane. The presequence translocase-associated motor (PAM) drives the completion of preprotein translocation into the matrix. Five subunits of PAM are known: the preprotein-binding matrix heat shock protein 70 (mtHsp70), the nucleotide exchange factor Mge1, Tim44 that directs mtHsp70 to the inner membrane, and the membrane-bound complex of Pam16-Pam18 that regulates the ATPase activity of mtHsp70. We have identified a sixth motor subunit. Pam17 (encoded by the open reading frame YKR065c) is anchored in the inner membrane and exposed to the matrix. Mitochondria lacking Pam17 are selectively impaired in the import of matrix proteins and the generation of an import-driving activity of PAM. Pam17 is required for formation of a stable complex between the cochaperones Pam16 and Pam18 and promotes the association of Pam16-Pam18 with the presequence translocase. Our findings suggest that Pam17 is required for the correct organization of the Pam16-Pam18 complex and thus contributes to regulation of mtHsp70 activity at the inner membrane translocation site.

scholarly journals Protein Disulfide Isomerase Superfamily in Disease and the Regulation of Apoptosis

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
C. Grek ◽  
D.M. Townsend
Keyword(s):  
Protein Folding ◽  
Er Stress ◽  
Cell Fate ◽  
Molecular Chaperones ◽  
Molecular Mechanisms ◽  
Disulfide Isomerases ◽  
Apoptotic Pathways ◽  
Er Homeostasis ◽  
Protein Disulfide

AbstractCellular homeostasis requires the balance of a multitude of signaling cascades that are contingent upon the essential proteins being properly synthesized, folded and delivered to appropriate subcellular locations. In eukaryotic cells the endoplasmic reticulum (ER) is a specialized organelle that is the central site of synthesis and folding of secretory, membrane and a number of organelletargeted proteins. The integrity of protein folding is enabled by the presence of ATP, Ca++, molecular chaperones, as well as an oxidizing redox environment. The imbalance between the load and capacity of protein folding results in a cellular condition known as ER stress. Failure of these pathways to restore ER homeostasis results in the activation of apoptotic pathways. Protein disulfide isomerases (PDI) compose a superfamily of oxidoreductases that have diverse sequences and are localized in the ER, nucleus, cytosol, mitochondria and cell membrane. The PDI superfamily has multiple functions including, acting as molecular chaperones, protein-binding partners, and hormone reservoirs. Recently , PDI family members have been implicated in the regulation of apoptotic signaling events. The complexities underlying the molecular mechanisms that define the switch from pro-survival to pro-death response are evidenced by recent studies that reveal the roles of specific chaperone proteins as integration points in signaling pathways that determine cell fate. The following review discusses the dual role of PDI in cell death and survival during ER stress.

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