Mitochondrial function in Parkinson's disease cybrids containing an nt2 neuron-like nuclear background.
Mitochondria likely play a role in Parkinson's disease (PD) neurodegeneration. We modelled PD by creating cytoplasmic hybrid (cybrid) cell lines in which endogenous mitochondrial DNA (mtDNA) from PD or control subject platelets was expressed within human teratocarcinoma (NT2) cells previously depleted of endogenous mtDNA. Complex I activity was reduced in both PD cybrid lines and in the platelet mitochondria used to generate them. Under basal conditions PD cybrids had less ATP, more LDH release, depolarized mitochondria, less mitochondrial cytochrome c, and higher caspase 3 activity. Equivalent MPP+ exposures are more likely to trigger programmed cell death in PD cybrid cells than in control cybrid cells. Our data support a relatively upstream role for mitochondrial dysfunction in idiopathic PD.
Esteves
A Raquel F
AR
Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Hospitais da Universidade de Coimbra, 3004 Coimbra, Portugal.
Domingues
A Filipa
AF
Ferreira
I Luísa
IL
Januário
Cristina
C
Swerdlow
Russell H
RH
Oliveira
Catarina R
CR
Cardoso
Sandra M
SM
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000032:analysis; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002950:Citrate (si)-Synthase / Q000032:analysis; D045304:Cytochromes c / Q000032:analysis; D004272:DNA, Mitochondrial / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006822:Hybrid Cells; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D018243:Teratocarcinoma / Q000473:pathology
D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D053148:Caspase 3; D015655:1-Methyl-4-phenylpyridinium