TIM23/YNR017W Summary Help

Standard Name TIM23 1
Systematic Name YNR017W
Alias MIM23 , MPI3 2 , MAS6 3
Feature Type ORF, Verified
Description Essential component of the TIM23 complex; involved in protein import into mitochondrial matrix and inner membrane; with Tim17p, contributes to architecture and function of the import channel; TIM23 complex is short for the translocase of the inner mitochondrial membrane (3, 4, 5 and see Summary Paragraph)
Name Description Translocase of the Inner Mitochondrial membrane 1
Chromosomal Location
ChrXIV:662913 to 663581 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All TIM23 GO evidence and references
  View Computational GO annotations for TIM23
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 4 genes
Resources
Classical genetics
conditional
null
reduction of function
repressible
Large-scale survey
conditional
null
overexpression
reduction of function
Resources
223 total interaction(s) for 49 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 21
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 141
  • Co-fractionation: 6
  • Co-localization: 1
  • Co-purification: 15
  • Far Western: 2
  • PCA: 1
  • Protein-peptide: 1
  • Reconstituted Complex: 16
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Rescue: 3
  • Negative Genetic: 4
  • Positive Genetic: 3
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 4

Resources
Expression Summary
histogram
Resources
Length (a.a.) 222
Molecular Weight (Da) 23,243
Isoelectric Point (pI) 7.43
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIV:662913 to 663581 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..669 662913..663581 2011-02-03 1997-01-28
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 SGDIDS000005300
SUMMARY PARAGRAPH for TIM23

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 6, 7 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 8, 7, 9). 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 (4), but Tim17p is required in vivo for maintenance of the twin-pore architecture and for normal function of the pore (5). Tim17p also has a role in sorting incoming proteins to the mitochondrial matrix or the inner membrane (10). Tim50p interacts with precursor proteins and with Tim23p to guide precursors from the TOM complex to the TIM23 complex (11, 12). Two additional non-essential components, Tim21p and Pam17p, interact with the core of the TIM23 complex and may modulate its activity (10, 13, 14).

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 (15, 16). Other components include Tim44p, an essential subunit that mediates the association of the core TIM23 complex with the PAM complex (17, 14); 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 (18). Pam17p mediates the association between Pam16p and Pam18p (19). 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 (20).

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 (8, 13).

About TIM23

TIM23 encodes an essential component of the core TIM23 complex (2, 3). The protein is anchored in the mitochondrial inner membrane with its four C-terminal transmembrane helices, which are capable of forming a voltage-sensitive translocation channel in vitro (4). The N-terminal domain is located in the intermembrane space (IMS), where it interacts with the receptor Tim50p (12). The N-terminal 20 residues of Tim23p are exposed on the surface of the mitochondrial outer membrane only during active preprotein translocation, suggesting that the conformation of the TIM23 complex and its association with the outer membrane are dynamic (21, 13). Tim23p together with Tim17p is likely responsible for the formation of the twin-pore, voltage-gated, and presequence-specific translocation channel, where Tim23p constitutes the primary structural component of the pore, and Tim17p supports the twin-pore structure and acts as a voltage sensor (5, 4). The gating of the channel formed by Tim23p and Tim17p appears also to be regulated by Tim50p; in the absence of translocation substrates, the IMS domain of Tim50p is capable of inducing the Tim23p pore to close, thus controlling the permeability of the mitochondrial inner membrane (22).

Last updated: 2009-03-17 Contact SGD

References cited on this page View Complete Literature Guide for TIM23
1) Pfanner N, et al.  (1996) Uniform nomenclature for the protein transport machinery of the mitochondrial membranes. Trends Biochem Sci 21(2):51-2
2) Dekker PJ, et al.  (1993) Identification of MIM23, a putative component of the protein import machinery of the mitochondrial inner membrane. FEBS Lett 330(1):66-70
3) Emtage JL and Jensen RE  (1993) MAS6 encodes an essential inner membrane component of the yeast mitochondrial protein import pathway. J Cell Biol 122(5):1003-12
4) 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
5) 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
6) Neupert W and Herrmann JM  (2007) Translocation of proteins into mitochondria. Annu Rev Biochem 76:723-49
7) 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
8) Wagner K, et al.  (2009) Protein transport machineries for precursor translocation across the inner mitochondrial membrane. Biochim Biophys Acta 1793(1):52-9
9) Bolender N, et al.  (2008) Multiple pathways for sorting mitochondrial precursor proteins. EMBO Rep 9(1):42-9
10) Chacinska A, et al.  (2005) Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell 120(6):817-29
11) 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
12) 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
13) Popov-Celeketic D, et al.  (2008) Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria. EMBO J 27(10):1469-80
14) 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
15) 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
16) Liu Q, et al.  (2003) Regulated cycling of mitochondrial Hsp70 at the protein import channel. Science 300(5616):139-41
17) 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
18) 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
19) 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
20) 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
21) Donzeau M, et al.  (2000) Tim23 links the inner and outer mitochondrial membranes. Cell 101(4):401-12
22) Meinecke M, et al.  (2006) Tim50 maintains the permeability barrier of the mitochondrial inner membrane. Science 312(5779):1523-6