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Review
. 2024 May;598(10):1170-1198.
doi: 10.1002/1873-3468.14792. Epub 2024 Jan 1.

Molecular mechanisms of perilipin protein function in lipid droplet metabolism

Elena Griseti  1 , Abdoul Akim Bello  2 , Eric Bieth  1   3 , Bayane Sabbagh  4 , Jason S Iacovoni  1 , Joëlle Bigay  2 , Henrik Laurell  1 , Alenka Čopič  4
Affiliations
Free article
Review

Molecular mechanisms of perilipin protein function in lipid droplet metabolism

Elena Griseti et al. FEBS Lett. 2024 May.
Free article

Abstract

Perilipins are abundant lipid droplet (LD) proteins present in all metazoans and also in Amoebozoa and fungi. Humans express five perilipins, which share a similar domain organization: an amino-terminal PAT domain and an 11-mer repeat region, which can fold into amphipathic helices that interact with LDs, followed by a structured carboxy-terminal domain. Variations of this organization that arose during vertebrate evolution allow for functional specialization between perilipins in relation to the metabolic needs of different tissues. We discuss how different features of perilipins influence their interaction with LDs and their cellular targeting. PLIN1 and PLIN5 play a direct role in lipolysis by regulating the recruitment of lipases to LDs and LD interaction with mitochondria. Other perilipins, particularly PLIN2, appear to protect LDs from lipolysis, but the molecular mechanism is not clear. PLIN4 stands out with its long repetitive region, whereas PLIN3 is most widely expressed and is used as a nascent LD marker. Finally, we discuss the genetic variability in perilipins in connection with metabolic disease, prominent for PLIN1 and PLIN4, underlying the importance of understanding the molecular function of perilipins.

Keywords: amphipathic helix; lipase; lipid droplet; lipodystrophy; lipolysis; metabolic disease; perilipin; perilipin phylogeny.

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