Parkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth
Familial Parkinson’s disease (PD) protein DJ-1 mutations are linked to early onset PD. We have found that DJ-1 binds directly to the F1FO ATP synthase β subunit. DJ-1’s interaction with the β subunit decreased mitochondrial uncoupling and enhanced ATP production efficiency while in contrast mutations in DJ-1 or DJ-1 knockout increased mitochondrial uncoupling, and depolarized neuronal mitochondria. In mesencephalic DJ-1 KO cultures, there was a progressive loss of neuronal process extension. This was ameliorated by a pharmacological reagent, dexpramipexole, that binds to ATP synthase, closing a mitochondrial inner membrane leak and enhancing ATP synthase efficiency. ATP synthase c-subunit can form an uncoupling channel; we measured, therefore, ATP synthase F1 (β subunit) and c-subunit protein levels. We found that ATP synthase β subunit protein level in the DJ-1 KO neurons was approximately half that found in their wild-type counterparts, comprising a severe defect in ATP synthase stoichiometry and unmasking c-subunit. We suggest that DJ-1 enhances dopaminergic cell metabolism and growth by its regulation of ATP synthase protein components.
|Persistent URL||dx.doi.org/10.1038/s41419-019-1679-x, hdl.handle.net/1765/117378|
|Journal||Cell Death and Disease|
Chen, R. (Rongmin), Park, H.-A. (Han-A), Mnatsakanyan, N. (Nelli), Niu, Y. (Yulong), Licznerski, P, Wu, J. (Jing), … Jonas, E.A. (Elizabeth A.). (2019). Parkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth. Cell Death and Disease, 10(6). doi:10.1038/s41419-019-1679-x