Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Neuronal hemoglobin in mitochondria is reduced by forming a complex with α-synuclein in aging monkey brains

Weiwei Yang, Xuran Li, Xin Li, Xuying Li and Shun Yu _

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Oncotarget. 2016; 7:7441-7454. https://doi.org/10.18632/oncotarget.7046

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Abstract

Weiwei Yang1,3, Xuran Li1,3, Xin Li1,3, Xuying Li1,3 and Shun Yu1,2,3

1 Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China

2 Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing, China

3 Beijing Key Laboratory for Parkinson’s Disease, Beijing, China

Correspondence to:

Shun Yu, email:

Keywords: aging, hemoglobin, α-synuclein, mitochondrion, Parkinson’s disease, Gerotarget

Received: January 16, 2016 Accepted: January 16, 2016 Published: January 27, 2016

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.


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