Mitochondria are a 'cell within a cell'. Their, relative to the complete cell, limited number of proteins, offer the opportunity to obtain, in the coming decade, an understanding of the processes that occur within them. Furthermore their evolutionary origin from a bacterium, the rapid accumulation of mitochondrial genomics data, and their relevance to human disease make them a very interesting subject for comparative analyses using bioinformatics techniques. We specifically focus on the prediction of the function of mitochondrial proteins and on the pathways that connect them. In the past we have e.g. correctly predicted a new protein involved in the oxidative phosphorylation Complex I and the involvement of the protein frataxin in the mitochondrial assembly of FeS clusters. Our current interests are into proteins involved in the response and defense against oxidative stress, in mitochondrial transport, in mitochondrial DNA maintenance and in the fission and fusion of mitochondria.

Recent publications

  1. The origin of the supernumerary subunits and assembly factors of complex I: A treasure trove of pathway evolution. Elurbe DM, Huynen MA. Biochim Biophys Acta. 2016 Apr 2. pii: S0005-2728(16)30074-3. doi: 10.1016/j.bbabio.2016.03.027. [Epub ahead of print] PubMed PMID: 27048931.

  2. Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex. Huynen MA, Mühlmeister M, Gotthardt K, Guerrero-Castillo S, Brandt U. Biochim Biophys Acta. 2015 Oct 15. pii: S0167-4889(15)00362-6.

  3. Transcriptome analysis of complex I-deficient patients reveals distinct expression programs for subunits and assembly factors of the oxidative phosphorylation system.van der Lee R, Szklarczyk R, Smeitink J, Smeets HJ, Huynen MA, Vogel R. BMC Genomics. 2015 Sep 15;16(1):691.

  4. A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly, activity and cytochrome b stability. Wanschers BF, Szklarczyk R, van den Brand MA, Jonckheere A, Suijskens J, Smeets R, Rodenburg RJ, Stephan K, Helland IB, Elkamil A, Rootwelt T, Ott M, van den Heuvel L, Nijtmans LG, Huynen MA. Hum Mol Genet. 2014 Dec 1;23(23):6356-65.

  5. The symbiotic intestinal ciliates and the evolution of their hosts. Moon-van der Staay SY, van der Staay GW, Michalowski T, Jouany JP, Pristas P, Javorský P, Kišidayová S, Varadyova Z, McEwan NR, Newbold CJ, van Alen T, de Graaf R, Schmid M, Huynen MA, Hackstein JH. Eur J Protistol. 2014 Apr;50(2):166-73.

  6. Mutations in the UQCC1-interacting protein, UQCC2, cause human complex III deficiency associated with perturbed cytochrome b protein expression. Tucker EJ, Wanschers BF, Szklarczyk R, Mountford HS, Wijeyeratne XW, van den Brand MA, Leenders AM, Rodenburg RJ, Reljić B, Compton AG, Frazier AE, Bruno DL, Christodoulou J, Endo H, Ryan MT, Nijtmans LG, Huynen MA, Thorburn DR. PLoS Genet. 2013;9(12):e1004034.

  7. Human intellectual disability genes form conserved functional modules in Drosophila. Oortveld MA, Keerthikumar S, Oti M, Nijhof B, Fernandes AC, Kochinke K, Castells-Nobau A, van Engelen E, Ellenkamp T, Eshuis L, Galy A, van Bokhoven H, Habermann B, Brunner HG, Zweier C, Verstreken P, Huynen MA, Schenck A. PLoS Genet. 2013 Oct;9(10):e1003911.

  8. Genome evolution predicts genetic interactions in protein complexes and reveals cancer drug targets. Lu X, Kensche PR, Huynen MA, Notebaart RA. Nat Commun. 2013;4:2124.

  9. optGpSampler: an improved tool for uniformly sampling the solution-space of genome-scale metabolic networks. Megchelenbrink W, Huynen M, Marchiori E. PLoS One. 2014 Feb 14;9(2):e86587.