Dopamine modulates mitochondrial function in viable SH-SY5Y cells possibly via its interaction with complex I: Relevance to dopamine pathology in schizophrenia

Hanit Brenner-Lavie, Ehud Klein, Rosa Zuk, Haifa Gazawi, Predrage Ljubuncic, Dorit Ben-Shachar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Deleterious effects of dopamine (DA) involving mitochondrial dysfunction have an important role in DA-associated neuronal disorders, including schizophrenia and Parkinson's disease. DA detrimental effects have been attributed to its ability to be auto-oxidized to toxic reactive oxygen species. Since, unlike Parkinson's disease, schizophrenia does not involve neurodegenerative processes, we suggest a novel mechanism by which DA impairs mitochondrial function without affecting cell viability. DA significantly dissipated mitochondrial membrane potential (Δψm) in SH-SY5Y cells. Bypassing complex I prevented the DA-induced depolarization. Moreover, DA inhibited complex I but not complex II activity in disrupted mitochondria, suggesting complex I participation in DA-induced mitochondrial dysfunction. We further demonstrated that intact mitochondria can accumulate DA in a saturated manner, with an apparent Km = 122.1 ± 28.6 nM and Vmax = 1.41 ± 0.15 pmol/mg protein/min, thereby enabling the interaction between DA and complex I. DA accumulation was an energy and Na+-dependent process. The pharmacological profile of mitochondrial DA uptake differed from that of other characterized DA transporters. Finally, relevance to schizophrenia is demonstrated by an abnormal interaction between DA and complex I in schizophrenic patients. These results suggest a non-lethal interaction between DA and mitochondria possibly via complex I, which can better explain DA-related pathological processes observed in non-degenerative disorders, such as schizophrenia.

Original languageEnglish
Pages (from-to)173-185
Number of pages13
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1777
Issue number2
DOIs
StatePublished - Feb 2008
Externally publishedYes

Funding

FundersFunder number
Center for Absorption in Science
Chief Scientist Israel Ministry of Health
Ministry of Aliyah and Immigrant Absorption

    Keywords

    • Complex I
    • Dopamine
    • Mitochondria
    • Mitochondrial dopamine uptake
    • Mitochondrial membrane potential
    • Schizophrenia

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