Respiratory function in cybrid cell lines carrying European mtDNA haplogroups: implications for Leber's hereditary optic neuropathy.
The possibility that some combinations of mtDNA polymorphisms, previously associated with Leber's hereditary optic neuropathy (LHON), may affect mitochondrial respiratory function was tested in osteosarcoma-derived transmitochondrial cytoplasmic hybrids (cybrids). In this cellular system, in the presence of the same nuclear background, different exogenous mtDNAs are used to repopulate a parental cell line previously devoid of its original mtDNA. No detectable differences in multiple parameters exploring respiratory function were observed when mtDNAs belonging to European haplogroups X, H, T and J were used. Different possible explanations for the previously established association between haplogroup J and LHON 11778/ND4 and 14484/ND6 pathogenic mutations are discussed, including the unconventional proposal that mtDNA haplogroup J may exert a protective rather than detrimental effect.
Carelli
Valerio
V
Istituto di Clinica Neurologica, Università di Bologna, Bologna, Italy.
Vergani
Lodovica
L
Bernazzi
Barbara
B
Zampieron
Claudia
C
Bucchi
Laura
L
Valentino
Maria
M
Rengo
Chiara
C
Torroni
Antonio
A
Martinuzzi
Andrea
A
D002999:Clone Cells; D003470:Culture Media; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D042967:Electron Transport Complex I; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005060:Europe; D006801:Humans; D006822:Hybrid Cells; D009154:Mutation; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012402:Rotenone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003470:Culture Media; D004272:DNA, Mitochondrial; D004791:Enzyme Inhibitors; D012402:Rotenone; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I