MGE1/YOR232W Summary Help

Standard Name MGE1 1
Systematic Name YOR232W
Alias YGE1 2
Feature Type ORF, Verified
Description Mitochondrial matrix cochaperone; nucleotide release factor for Ssc1p in protein translocation and folding; also acts as cochaperone for Ssq1p in folding of Fe-S cluster proteins; acts as oxidative sensor to regulate mitochondrial Ssc1p; in presence of oxidative stress, dimeric Mge1p becomes a monomer and unable to regulate Ssc1p function; homolog of E. coli GrpE and human Mge1 (GRPEL1), which also responds to oxidative stress (1, 2, 3, 4, 5, 6, 7 and see Summary Paragraph)
Also known as: GRPE 5
Name Description Mitochondrial GrpE 1
Chromosomal Location
ChrXV:774573 to 775259 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All MGE1 GO evidence and references
  View Computational GO annotations for MGE1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 4 genes
Resources
Classical genetics
conditional
null
overexpression
repressible
unspecified
Large-scale survey
null
overexpression
reduction of function
repressible
unspecified
Resources
141 total interaction(s) for 111 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 13
  • Affinity Capture-RNA: 5
  • Affinity Capture-Western: 20
  • Biochemical Activity: 1
  • Co-fractionation: 1
  • Co-purification: 4
  • Protein-peptide: 1
  • Reconstituted Complex: 6
  • Two-hybrid: 19

Genetic Interactions
  • Dosage Lethality: 1
  • Negative Genetic: 58
  • Positive Genetic: 5
  • Synthetic Lethality: 7

Resources
Expression Summary
histogram
Resources
Length (a.a.) 228
Molecular Weight (Da) 26,066
Isoelectric Point (pI) 8.9
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:774573 to 775259 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..687 774573..775259 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005758
SUMMARY PARAGRAPH for MGE1

About mitochondrial import

While the mitochondrial genome encodes a handful of proteins, most of the hundreds of proteins that reside in the mitochondrion are encoded by nuclear genes, translated in the cytoplasm, and imported into mitochondria via a series of complex molecular machines (see 8, 9 for review). Many of the proteins imported into mitochondria are involved in respiration, which is not an essential process: S. cerevisiae is able to carry out either fermentative growth on carbon sources such as glucose, or respiratory growth on nonfermentable carbon sources such as glycerol and ethanol. However, since maintenance of the mitochondrial compartment is essential to life, mutations that completely disrupt mitochondrial import are lethal.

About the TIM23 complex

The Translocase of the Inner Mitochondrial membrane (TIM23 complex) receives proteins from the Translocase of the Outer Mitochondrial membrane (TOM complex) and either directs them into the mitochondrial matrix or facilitates their integration into the mitochondrial inner membrane (reviewed in 10, 9, 11). The membrane-embedded core of the complex is composed of three essential proteins: Tim23p, Tim17p, and Tim50p. Tim23p and Tim17p, which share sequence similarity, comprise the twin-pore structure through which precursor proteins translocate. Tim23p alone has the ability to form a voltage-sensitive channel (12), but Tim17p is required in vivo for maintenance of the twin-pore architecture and for normal function of the pore (13). Tim17p also has a role in sorting incoming proteins to the mitochondrial matrix or the inner membrane (14). Tim50p interacts with precursor proteins and with Tim23p to guide precursors from the TOM complex to the TIM23 complex (15, 16). Two additional non-essential components, Tim21p and Pam17p, interact with the core of the TIM23 complex and may modulate its activity (14, 17, 18).

Proteins destined for the mitochondrial matrix require the action of a sub-complex of the TIM23 complex, known as the import motor or presequence translocase-associated motor (PAM) complex. Its catalytic component is Ssc1p, a member of the heat shock 70 protein family commonly referred to as mtHsp70, which undergoes cycles of binding and release of the precursor, hydrolyzing ATP and changing conformation in the process. The nucleotide release factor Mge1p promotes this cycle by facilitating the dissociation of ADP from Ssc1p (19, 20). Other components include Tim44p, an essential subunit that mediates the association of the core TIM23 complex with the PAM complex (21, 18); Pam18p (Tim14p), a J-protein cochaperone that stimulates the ATPase activity of Ssc1p; and Pam16p (Tim16p), a J-like protein that binds to Pam18p and regulates its activity (22). Pam17p mediates the association between Pam16p and Pam18p (23). Once imported proteins reach the mitochondrial matrix, their correct folding is facilitated by a soluble complex consisting of Ssc1p and its cochaperones Mdj1p and Mge1p (24).

A subset of proteins destined for insertion into the mitochondrial inner membrane is translocated via the TIM23 complex but then inserted laterally into the inner membrane rather than entering the mitochondrial matrix. This mechanism is currently not understood in detail. The TIM23 complex adopts different conformations during the two kinds of import, but it is unclear whether this inner membrane import is accomplished by the core complex alone (Tim23p, Tim17p, and Tim50p), or by the entire TIM23 complex including the import motor subunits (10, 17).

About MGE1

MGE1 encodes an essential protein of the mitochondrial matrix that is a sequence and functional homolog of E. coli GrpE (5, 25, 1, 3). Mge1p and related proteins act as nucleotide release factors for chaperones of the Hsp70 family: after ATP hydrolysis by the chaperone, the nucleotide release factor promotes the dissociation of ADP, allowing the binding and hydrolysis of another ATP molecule (4, 26, 19, 20). Mge1p promotes ADP release from Ssc1p in the import motor complex, allowing the cycle of ATP-dependent protein translocation to proceed (19, 20). Certain conditional mge1 mutations affect its function in import (27, 28). Mge1p also acts in a soluble complex in the mitochondrial matrix, with Ssc1p and the J-protein Mdj1p, that re-folds denatured proteins (28, 29, 24). In addition, Mge1p functions as a nucleotide release factor for the Hsp70 family chaperone Ssq1p, which facilitates the folding of proteins containing iron-sulfur clusters (6).

Last updated: 2009-03-17 Contact SGD

References cited on this page View Complete Literature Guide for MGE1
1) Laloraya S, et al.  (1994) A role for a eukaryotic GrpE-related protein, Mge1p, in protein translocation. Proc Natl Acad Sci U S A 91(14):6481-5
2) Ikeda E, et al.  (1994) YGE1 is a yeast homologue of Escherichia coli grpE and is required for maintenance of mitochondrial functions. FEBS Lett 339(3):265-8
3) Deloche O and Georgopoulos C  (1996) Purification and biochemical properties of Saccharomyces cerevisiae's Mge1p, the mitochondrial cochaperone of Ssc1p. J Biol Chem 271(39):23960-6
4) Miao B, et al.  (1997) Mge1 functions as a nucleotide release factor for Ssc1, a mitochondrial Hsp70 of Saccharomyces cerevisiae. J Mol Biol 265(5):541-52
5) Bolliger L, et al.  (1994) A mitochondrial homolog of bacterial GrpE interacts with mitochondrial hsp70 and is essential for viability. EMBO J 13(8):1998-2006
6) Schmidt S, et al.  (2001) The two mitochondrial heat shock proteins 70, Ssc1 and Ssq1, compete for the cochaperone Mge1. J Mol Biol 313(1):13-26
7) Marada A, et al.  (2013) Mge1, a nucleotide exchange factor of Hsp70, acts as an oxidative sensor to regulate mitochondrial Hsp70 function. Mol Biol Cell 24(6):692-703
8) Neupert W and Herrmann JM  (2007) Translocation of proteins into mitochondria. Annu Rev Biochem 76:723-49
9) Mokranjac D and Neupert W  (2009) Thirty years of protein translocation into mitochondria: unexpectedly complex and still puzzling. Biochim Biophys Acta 1793(1):33-41
10) Wagner K, et al.  (2009) Protein transport machineries for precursor translocation across the inner mitochondrial membrane. Biochim Biophys Acta 1793(1):52-9
11) Bolender N, et al.  (2008) Multiple pathways for sorting mitochondrial precursor proteins. EMBO Rep 9(1):42-9
12) Truscott KN, et al.  (2001) A presequence- and voltage-sensitive channel of the mitochondrial preprotein translocase formed by Tim23. Nat Struct Biol 8(12):1074-82
13) Martinez-Caballero S, et al.  (2007) Tim17p regulates the twin pore structure and voltage gating of the mitochondrial protein import complex TIM23. J Biol Chem 282(6):3584-93
14) Chacinska A, et al.  (2005) Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell 120(6):817-29
15) Mokranjac D, et al.  (2009) Role of Tim50 in the transfer of precursor proteins from the outer to the inner membrane of mitochondria. Mol Biol Cell 20(5):1400-7
16) Gevorkyan-Airapetov L, et al.  (2009) Interaction of Tim23 with Tim50 Is Essential for Protein Translocation by the Mitochondrial TIM23 Complex. J Biol Chem 284(8):4865-72
17) Popov-Celeketic D, et al.  (2008) Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria. EMBO J 27(10):1469-80
18) Hutu DP, et al.  (2008) Mitochondrial protein import motor: differential role of tim44 in the recruitment of pam17 and j-complex to the presequence translocase. Mol Biol Cell 19(6):2642-9
19) Schneider HC, et al.  (1996) The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import. EMBO J 15(21):5796-803
20) Liu Q, et al.  (2003) Regulated cycling of mitochondrial Hsp70 at the protein import channel. Science 300(5616):139-41
21) D'Silva P, et al.  (2004) Regulated interactions of mtHsp70 with Tim44 at the translocon in the mitochondrial inner membrane. Nat Struct Mol Biol 11(11):1084-91
22) Mokranjac D, et al.  (2006) Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor. EMBO J 25(19):4675-85
23) Van Der Laan M, et al.  (2005) Pam17 is required for architecture and translocation activity of the mitochondrial protein import motor. Mol Cell Biol 25(17):7449-58
24) Kubo Y, et al.  (1999) Two distinct mechanisms operate in the reactivation of heat-denatured proteins by the mitochondrial Hsp70/Mdj1p/Yge1p chaperone system. J Mol Biol 286(2):447-64
25) Voos W, et al.  (1994) Mitochondrial GrpE is present in a complex with hsp70 and preproteins in transit across membranes. Mol Cell Biol 14(10):6627-34
26) Dekker PJ and Pfanner N  (1997) Role of mitochondrial GrpE and phosphate in the ATPase cycle of matrix Hsp70. J Mol Biol 270(3):321-7
27) Westermann B, et al.  (1995) The role of the GrpE homologue, Mge1p, in mediating protein import and protein folding in mitochondria. EMBO J 14(14):3452-60
28) Laloraya S, et al.  (1995) Mitochondrial GrpE modulates the function of matrix Hsp70 in translocation and maturation of preproteins. Mol Cell Biol 15(12):7098-105
29) Horst M, et al.  (1997) Sequential action of two hsp70 complexes during protein import into mitochondria. EMBO J 16(8):1842-9