Table: Diseases with suggested mitochondrial connection
Yeast ORF Description Human homologue (GenBank) Blast E-value Disease OMIM entry Proposed pathophysiological link to mito.
YGL167C (PMR1) Ca2+-transporting P-type ATPase ATP2C1 (AF189723) 0 Benign chronic pemphigus; Hailey-Hailey disease (HHD) 604384 Defects in a paralog to ATP2C1 causes Darier disease, characterized by shrinkage and densification of mitochondria1
YMR167W (MLH1) DNA mismatch repair protein MLH1 (NM_000249) 10-130 Colorectal cancer, hereditary nonpolyposis, type 2, HNPCC2 120436 Possible apoptosis defect2,3
YAL012W (CYS3) cystathionine gamma-lyase CTH (NM_001902) 10-103 Cystathioninuria 219500 Elevated levels of homocysteine in MTHFR defects result in bizarre, giant mitochondria4 and its accumulation may have similar effect in CTH mutants
YGR155W (CYS4) cystathionine beta-synthase CBS (NM_000071) 8x10-87 Homocystinuria, B6-responsive and nonresponsive types 236200 Elevated levels of homocysteine in MTHFR defects result in bizarre, giant mitochondria4 and its accumulation may have similar effect in CBS mutants
YJR040W (GEF1) Voltage-gated chloride channel protein CLCN5 (NM_000084) 3x10-85 Dent disease; Fanconi syndrome renal, with Nephrocalcinosis and renal stones, NPHL2 300008 Defects in chloride homeostasis in CLCN5 mutants may lead to cellular copper accumulation5, which may affect mitochondrial copper levels
YOL081W (IRA2) GTPase-activating protein for RAS proteins NFI (NM_000267) 3x10-60 Neurofibromatosis, type 1; (NF1) von Recklinghausen, Watson disease 162200 Possible apoptosis defect2,3
YGL115W (SNF4) Nuclear regulatory protein, derepression of glucose repressed genes PRKAG2 (AK001887) 6x10-41 Wolff-Parkinson-White syndrome, cardiomyopathy, familial hypertrophic 602743 Defects in PRKAG2 have associated with abnormal ATP levels6
YBR289W (SNF5) component of SWI/SNF transcription activator complex SMARCB1 (NM_003073) 5x10-18 Predisposition to malignant rhabdoid tumors (MRT), brain tumor, posterior fossa of infancy, familial 601607 Possible apoptosis defect2,3
  1. Mesquita-Guimaraes, J. & Mesquita-Guimaraes, I. Cellular differentiation in Darier's disease. Ultrastructural aspects. J. Submicrosc. Cytol. 16, 387-394 (1984).

  2. Hardman, R.A., Afshari, C.A. & Barrett, J.C. Involvement of mammalian MLH1 in the apoptotic response to peroxide-induced oxidative stress. Cancer Res. 61, 1392-1397 (2001).

  3. Wallace, D.C. Mitochondrial diseases in man and mouse. Science 283, 1482-1488 (1999).

  4. Kanwar, Y.S., Manaligod, J.R. & Wong, P.W. Morphologic studies in a patient with homocystinuria due to 5, 10-methylenetetrahydrofolate reductase deficiency. Pediatr. Res. 10, 598-609 (1976).

  5. Davis-Kaplan, S.R., Askwith, C.C., Bengtzen, A.C., Radisky, D. & Kaplan, J. Chloride is an allosteric effector of copper assembly for the yeast multicopper oxidase Fet3p: an unexpected role for intracellular chloride channels. Proc. Natl. Acad. Sci. USA 95, 13641-13645 (1998).

  6. Blair, E. et al. Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. Hum. Mol. Genet. 10, 1215-1220 (2001).