The murine retinal pigment epithelium requires peroxisomal β-oxidation to maintain lysosomal function and prevent dedifferentiation.
lipids
lysosomes
peroxisomes
retinal degeneration
retinal pigment epithelium
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
24 Oct 2023
24 Oct 2023
Historique:
pmc-release:
20
04
2024
medline:
1
11
2023
pubmed:
20
10
2023
entrez:
20
10
2023
Statut:
ppublish
Résumé
Retinal pigment epithelium (RPE) cells have to phagocytose shed photoreceptor outer segments (POS) on a daily basis over the lifetime of an organism, but the mechanisms involved in the digestion and recycling of POS lipids are poorly understood. Although it was frequently assumed that peroxisomes may play an essential role, this was never investigated. Here, we show that global as well as RPE-selective loss of peroxisomal β-oxidation in multifunctional protein 2 (MFP2) knockout mice impairs the digestive function of lysosomes in the RPE at a very early age, followed by RPE degeneration. This was accompanied by prolonged mammalian target of rapamycin activation, lipid deregulation, and mitochondrial structural anomalies without, however, causing oxidative stress or energy shortage. The RPE degeneration caused secondary photoreceptor death. Notably, the deterioration of the RPE did not occur in an
Identifiants
pubmed: 37862382
doi: 10.1073/pnas.2301733120
pmc: PMC10614831
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2301733120Subventions
Organisme : KU Leuven (Katholieke Universiteit Leuven)
ID : C14/18/088
Organisme : Fonds Wetenschappelijk Onderzoek (FWO)
ID : FWO G0A8619N
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