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Parkin in the regulation of fat uptake and mitochondrial biology: emerging links in the pathophysiology of Parkinson's disease

Kim, Kye-Young; Sack, Michael N.

Current Opinion in Lipidology: June 2012 - Volume 23 - Issue 3 - p 201–205
doi: 10.1097/MOL.0b013e328352dc5d
LIPID METABOLISM: Edited by Jeffrey S. Cohn
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Purpose of review Perturbations in fatty acid levels and in regulatory proteins linked to fat and mitochondrial homeostasis are associated with modifying the risk of Parkinson's disease . Findings, that are not surprising, based on the high fat content of the brain, the myriad of neurological functions dependent on polyunsaturated fatty acids and the role of mitochondria in energy supply and stress amelioration. Nevertheless, dissecting out the molecular links between lipid biology, mitochondrial regulation and Parkinson's disease is complicated by the divergent causes underpinning Parkinson's disease pathophysiology. Here, we summarize aspects of fatty acid biology relevant to Parkinson's disease; the known links between the modulation of fat and Parkinson's disease and introduce mechanisms whereby the E3-ubiquitin ligase, Parkin known to be mutated as a genetic predisposing factor in Parkinson's disease, modulates fat uptake and mitochondrial control.

Recent findings Prior evidence supports that Parkin, under mitochondrial stress conditions, plays a pivotal role in the mitophagy mitochondrial housekeeping program. Recent evidence now demonstrates a broader role of Parkin in controlling fat uptake and mitochondrial regulatory programs.

Summary The identification that Parkin has a multifunctional role in modulating cellular fatty acid uptake and mitochondrial biology further strengthens the pathophysiologic link between fat metabolism, mitochondria and Parkinson's disease.

Center for Molecular Medicine, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA

Correspondence to Michael N. Sack, 10-CRC Room 5-3150, 10 Center Drive, Bethesda, MD 20892-1454, USA. Tel: +1 301 402 9259; e-mail: sackm@nhlbi.nih.gov

© 2012 Lippincott Williams & Wilkins, Inc.