Xenomitochondrial mice: Investigation into mitochondrial compensatory mechanisms |
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| Authors: | MV Cannon DA Dunn MH Irwin AI Brooks FF Bartol IA Trounce CA Pinkert |
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| Institution: | 1. Department of Pathobiology, College of Veterinary Medicine, Auburn University, Alabama 36849, United States;2. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester NY 14534, United States;3. Department of Environmental Medicine and Genetics, Environmental and Occupational Health Science Institute, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, United States;4. Department Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Alabama 36849, United States;5. Center for Eye Research Australia, Department of Ophthalmology University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisborne St., East Melbourne, Victoria 3002, Australia;1. The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China;2. Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China;3. Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA;1. Natural Sciences and Mathematics, Chaminade University of Honolulu, 3140 Waialae Ave, Honolulu, HI 96816, USA;2. Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo St., Honolulu, HI 96813, USA;3. Obstetrics, Gynecology and Women''s Health, John A. Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo St., Honolulu, HI 96813, USA;1. Department of Veterinary Physiology, Northeast Agricultural University, Harbin 150030, PR China;2. Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China;1. Department of Medicine, University of Washington, Harborview Medical Center, 325 9th Ave., Seattle, WA 98104, United States;2. Hope Heart Matrix Biology Program, Benaroya Research Institute at Virginia Mason, 1201 9th Ave., Seattle, WA 98101-2795, United States;1. Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA;2. Department of Bioengineering, University of California, Los Angeles, CA 90095, USA;3. California NanoSystems Institute, University of California, Los Angeles, CA 90095, USA;4. Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA 90095, USA;5. Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA |
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| Abstract: | Xenomitochondrial mice, harboring evolutionarily divergent Mus terricolor mitochondrial DNA (mtDNA) on a Mus musculus domesticus nuclear background (B6NTac(129S6)-mtM. terricolor/Capt; line D7), were subjected to molecular and phenotypic analyses. No overt in vivo phenotype was identified in contrast to in vitro xenomitochondrial cybrid studies. Microarray analyses revealed differentially expressed genes in xenomitochondrial mice, though none were directly involved in mitochondrial function. qRT-PCR revealed upregulation of mt-Co2 in xenomitochondrial mice. These results illustrate that cellular compensatory mechanisms for mild mitochondrial dysfunction alter mtDNA gene expression at a proteomic and/or translational level. Understanding these mechanisms will facilitate the development of therapeutics for mitochondrial disorders. |
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