Metabolic-scale gene activation screens identify SLCO2B1 as a heme transporter that enhances cellular iron availability.
CRISPRa
SLCO2B1
heme
iron
metabolic limitation
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
04 08 2022
04 08 2022
Historique:
received:
23
01
2022
revised:
14
04
2022
accepted:
18
05
2022
pubmed:
18
6
2022
medline:
10
8
2022
entrez:
17
6
2022
Statut:
ppublish
Résumé
Iron is the most abundant transition metal essential for numerous cellular processes. Although most mammalian cells acquire iron through transferrin receptors, molecular players of iron utilization under iron restriction are incompletely understood. To address this, we performed metabolism-focused CRISPRa gain-of-function screens, which revealed metabolic limitations under stress conditions. Iron restriction screens identified not only expected members of iron utilization pathways but also SLCO2B1, a poorly characterized membrane carrier. SLCO2B1 expression is sufficient to increase intracellular iron, bypass the essentiality of the transferrin receptor, and enable proliferation under iron restriction. Mechanistically, SLCO2B1 mediates heme analog import in cellular assays. Heme uptake by SLCO2B1 provides sufficient iron for proliferation through heme oxygenases. Notably, SLCO2B1 is predominantly expressed in microglia in the brain, and primary Slco2b1
Identifiants
pubmed: 35714613
pii: S1097-2765(22)00491-9
doi: 10.1016/j.molcel.2022.05.024
pmc: PMC9356996
mid: NIHMS1810724
pii:
doi:
Substances chimiques
Membrane Transport Proteins
0
Organic Anion Transporters
0
Slco2b1 protein, mouse
0
Heme
42VZT0U6YR
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2832-2843.e7Subventions
Organisme : NCI NIH HHS
ID : DP2 CA228042
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123323
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001866
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests K.B. is a scientific advisor to Nanocare Pharmaceuticals and Barer Institute.
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