TIM10/YHR005C-A Summary Help

Standard Name TIM10 1
Systematic Name YHR005C-A
Alias MRS11 2
Feature Type ORF, Verified
Description Essential protein of the mitochondrial intermembrane space; forms a complex with Tim9p (TIM10 complex) that delivers hydrophobic proteins to the TIM22 complex for insertion into the inner membrane (2, 3, 4 and see Summary Paragraph)
Name Description Translocase of the Inner Membrane 1
Chromosomal Location
ChrVIII:115901 to 115620 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All TIM10 GO evidence and references
  View Computational GO annotations for TIM10
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 7 genes
Classical genetics
reduction of function
Large-scale survey
reduction of function
51 total interaction(s) for 23 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 2
  • Affinity Capture-RNA: 5
  • Affinity Capture-Western: 12
  • Biochemical Activity: 2
  • Co-fractionation: 2
  • Co-purification: 16
  • Reconstituted Complex: 8

Genetic Interactions
  • Synthetic Lethality: 2
  • Synthetic Rescue: 2

Expression Summary
Length (a.a.) 93
Molecular Weight (Da) 10,305
Isoelectric Point (pI) 5.13
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrVIII:115901 to 115620 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1999-07-17
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..282 115901..115620 2011-02-03 1999-07-17
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003530

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 5, 6 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 TIM22 complex

The TIM22 complex of the mitochondrial inner membrane mediates the insertion of large hydrophobic proteins, typically transporters (carrier proteins) with multiple transmembrane segments, into the inner membrane. These proteins travel through the outer membrane via the translocase of the outer mitochondrial membrane (TOM) complex. Their transit across the intermembrane space to the TIM22 complex in the inner membrane is mediated by complexes of small soluble protein chaperones: Tim8p with Tim13p, and Tim9p with Tim10p. The membrane-embedded core of the TIM22 complex consists of Tim54p, Tim22p, Tim18p, and Sdh3p (7); additionally, the small Tim proteins Tim9p, Tim10p, and Tim12p are associated with the complex on the intermembrane space side (reviewed in 8, 6).

About the small Tim proteins

Five small (87-109 amino acids), related proteins involved in mitochondrial import (Tim8p, Tim9p, Tim10p, Tim12p, and Tim13p, collectively referred to as the small Tim proteins) reside in the mitochondrial intermembrane space.

Tim9p and Tim10p, both essential proteins, form a soluble hexameric complex consisting of three molecules each of Tim9p and Tim10p that displays protein refolding activity (9, 4). The Tim9p-Tim10p complex assembles into a soluble complex with Tim12p, which then docks onto the TIM22 complex (10). Incoming carrier proteins bind to the Tim9p-Tim10p-Tim12p complex that is peripherally associated with the TIM22 complex, and are subsequently inserted into the inner membrane (3, 11, 9, 4, 10). There is also evidence that the Tim9p-Tim10p complex is involved in import of integral outer membrane proteins, mediating their transfer between the translocase of the outer mitochondrial membrane (TOM) complex and the sorting and assembly machinery (SAM) complex (12). Conditional mutants of each of the three essential small TIM genes (TIM9, TIM10, and TIM12) display a petite-negative phenotype: loss of the mitochondrial genome is lethal to the mutant strains (13).

The two nonessential small Tim proteins, Tim8p and Tim13p, form a soluble complex with each other (14). The tim8 null mutation is synthetically lethal with a conditional tim10 mutation, suggesting that the two Tim complexes functionally interact (14). Genetic and physical evidence suggests that the Tim8p-Tim13p complex mediates the transit across the intermembrane space of a subset of proteins destined for the inner membrane (15, 16).

The small TIM proteins are evolutionarily conserved. Orthologs of each of the five S. cerevisiae genes are found in human; some organisms have fewer than five related genes (17). One of the human orthologs, TIMM8A or DDP1, is implicated in the neurodegenerative disorder Mohr-Tranebjaerg syndrome (OMIM), also known as dystonia-deafness syndrome (14, 18).

Last updated: 2009-03-17 Contact SGD

References cited on this page View Complete Literature Guide for TIM10
1) Sirrenberg C, et al.  (1998) Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5. Nature 391(6670):912-5
2) Jarosch E, et al.  (1997) A soluble 12-kDa protein of the mitochondrial intermembrane space, Mrs11p, is essential for mitochondrial biogenesis and viability of yeast cells. Mol Gen Genet 255(2):157-65
3) Koehler CM, et al.  (1998) Tim9p, an essential partner subunit of Tim10p for the import of mitochondrial carrier proteins. EMBO J 17(22):6477-86
4) Vial S, et al.  (2002) Assembly of Tim9 and Tim10 into a functional chaperone. J Biol Chem 277(39):36100-8
5) Neupert W and Herrmann JM  (2007) Translocation of proteins into mitochondria. Annu Rev Biochem 76:723-49
6) 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
7) Gebert N, et al.  (2011) Dual Function of Sdh3 in the Respiratory Chain and TIM22 Protein Translocase of the Mitochondrial Inner Membrane. Mol Cell 44(5):811-8
8) Bolender N, et al.  (2008) Multiple pathways for sorting mitochondrial precursor proteins. EMBO Rep 9(1):42-9
9) Curran SP, et al.  (2002) The Tim9p-Tim10p complex binds to the transmembrane domains of the ADP/ATP carrier. EMBO J 21(5):942-53
10) Gebert N, et al.  (2008) Assembly of the three small Tim proteins precedes docking to the mitochondrial carrier translocase. EMBO Rep 9(6):548-54
11) Adam A, et al.  (1999) Tim9, a new component of the TIM22.54 translocase in mitochondria. EMBO J 18(2):313-9
12) Wiedemann N, et al.  (2004) Biogenesis of the protein import channel Tom40 of the mitochondrial outer membrane: intermembrane space components are involved in an early stage of the assembly pathway. J Biol Chem 279(18):18188-94
13) Senapin S, et al.  (2003) Transcription of TIM9, a new factor required for the petite-positive phenotype of Saccharomyces cerevisiae, is defective in spt7 mutants. Curr Genet 44(4):202-10
14) Koehler CM, et al.  (1999) Human deafness dystonia syndrome is a mitochondrial disease. Proc Natl Acad Sci U S A 96(5):2141-6
15) Leuenberger D, et al.  (1999) Different import pathways through the mitochondrial intermembrane space for inner membrane proteins. EMBO J 18(17):4816-22
16) Davis AJ, et al.  (2007) The Tim9p/10p and Tim8p/13p complexes bind to specific sites on Tim23p during mitochondrial protein import. Mol Biol Cell 18(2):475-86
17) Gentle IE, et al.  (2007) Conserved Motifs Reveal Details of Ancestry and Structure in the Small TIM Chaperones of the Mitochondrial Intermembrane Space. Mol Biol Evol 24(5):1149-60
18) Bauer MF, et al.  (1999) The mitochondrial TIM22 preprotein translocase is highly conserved throughout the eukaryotic kingdom. FEBS Lett 464(1-2):41-7