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Parkin reinvents itself to regulate fatty acid metabolism by tagging CD36
Nada A. Abumrad, Darren J. Moore
Nada A. Abumrad, Darren J. Moore
Published August 25, 2011
Citation Information: J Clin Invest. 2011;121(9):3389-3392. https://doi.org/10.1172/JCI59219.
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Commentary

Parkin reinvents itself to regulate fatty acid metabolism by tagging CD36

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Abstract

Parkinson disease (PD) is a relatively common neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. About 5%–10% of PD cases are inherited. Mutations in the Parkin gene, which encodes a protein that can function as an E3 ubiquitin ligase, are a common cause of familial PD. Such mutations act in a loss-of-function manner and impair the ability of the encoded protein to mediate substrate ubiquitination, although the subsequent molecular pathway that precipitates neuronal degeneration is poorly defined. In this issue of the JCI, Kim and colleagues describe painstaking evidence using a number of dissecting approaches in intact animals and cultured cells to functionally link Parkin and the class B scavenger receptor CD36, suggesting a novel and complex connection between PD and fatty acid metabolism.

Authors

Nada A. Abumrad, Darren J. Moore

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Figure 1

Substrates of Parkin-dependent ubiquitination.

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Substrates of Parkin-dependent ubiquitination.
Parkin contains a ubiquit...
Parkin contains a ubiquitin-like (Ubl) domain and a RING-box (RBR) domain consisting of two RING finger motifs separated by an in-between-RING finger domain (IBR). Parkin cooperates with E1-activating and E2-conjugating enzymes to covalently modify protein substrates with ubiquitin, either via alternatively linked polyubiquitin chains or via monoubiquitination. Polyubiquitination via K48-linked chains serves to target substrates for proteasomal degradation, whereas K63-linked polyubiquitination and monoubiquitination serve as nondegradative signals. A broad range of substrates is ubiquitinated by Parkin, often being targeted for degradation (i.e., PAEL-R, AIMP2/p38, CDCrel-1, and cyclin E), whereas others are degradation independent (i.e., Hsp70 and synphilin-1). The lipid transporter CD36 is the latest substrate identified for Parkin and is stabilized by monoubiquitination (7), providing a novel mechanism for the regulation of FA uptake.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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