title: Neuronal hemoglobin in mitochondria is reduced by forming a complex with α-synuclein in aging monkey brains.
abstract: Neuronal hemoglobin (nHb) plays a critical role in maintaining normal mitochondrial functioning in the brain. However, in aging and Parkinson's disease (PD) brains, mitochondrial nHb levels are greatly reduced in neurons that accumulate α-synuclein (α-syn), suggesting a link between the two proteins. In this study, we demonstrate that α-syn and Hb can form a complex in both brain tissue and peripheral red blood cells (RBCs) in aging cynomolgus monkeys. nHb-α-syn complex levels in the mitochondrial fraction of the striatum decreased with age; this was negatively correlated with levels in the cytoplasmic fraction and in RBCs and was accompanied by a reduction in mitochondrial free nHb. In contrast, no changes in nHb-α-syn complex formation or free nHb levels were detected in the cerebellum. In vitro studies using a cultured dopaminergic cell line showed that intracellular accumulation of α-syn caused an elevation in nHb-α-syn complex levels in both mitochondrial and cytoplasmic fractions as well as a reduction in mitochondrial free nHb. nHb overexpression increased free nHb levels in mitochondria, stabilized mitochondrial membrane potential, and reduced α-syn-induced apoptosis. The above results suggest that α-syn forms a complex with nHb in selected regions of the aging brain, thereby decreasing mitochondrial function and increasing the risk of PD.
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.|Beijing Key Laboratory for Parkinson's Disease, Beijing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.|Beijing Key Laboratory for Parkinson's Disease, Beijing, China.
authors.forename: Xuran
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.|Beijing Key Laboratory for Parkinson's Disease, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.|Beijing Key Laboratory for Parkinson's Disease, Beijing, China.
authors.forename: Xuying
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.|Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China.|Beijing Key Laboratory for Parkinson's Disease, Beijing, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Yu
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008252:Macaca fascicularis; D053078:Membrane Potential, Mitochondrial; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D006454:Hemoglobins; D051844:alpha-Synuclein
keywords: Gerotarget; Parkinson’s disease; aging; hemoglobin; mitochondrion; α-synuclein
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