Universität zu Köln

Tharyan, Rebecca George, Annibal, Andrea ORCID: 0000-0003-4311-5417, Schiffer, Isabelle, Laboy, Raymond ORCID: 0000-0002-0375-1550, Atanassov, Ilian ORCID: 0000-0001-8259-2545, Weber, Anna Luise, Gerisch, Birgit and Antebi, Adam (2020). NFYB-1 regulates mitochondrial function and longevity via lysosomal prosaposin. Nat. Metab., 2 (5). S. 387 - 406. BERLIN: NATURE RESEARCH. ISSN 2522-5812

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Abstract

Mitochondria are multidimensional organelles whose activities are essential to cellular vitality and organismal longevity, yet underlying regulatory mechanisms spanning these different levels of organization remain elusive(1-5). Here we show that Caenorhabditis elegans nuclear transcription factor Y, beta subunit (NFYB-1), a subunit of the NF-Y transcriptional complex(6-8), is a crucial regulator of mitochondrial function. Identified in RNA interference (RNAi) screens, NFYB-1 loss leads to perturbed mitochondrial gene expression, reduced oxygen consumption, mitochondrial fragmentation, disruption of mitochondrial stress pathways, decreased mitochondrial cardiolipin levels and abolition of organismal longevity triggered by mitochondrial impairment. Multi-omics analysis reveals that NFYB-1 is a potent repressor of lysosomal prosaposin, a regulator of glycosphingolipid metabolism. Limiting prosaposin expression unexpectedly restores cardiolipin production, mitochondrial function and longevity in the nfyb-1 background. Similarly, cardiolipin supplementation rescues nfyb-1 phenotypes. These findings suggest that the NFYB-1-prosaposin axis coordinates lysosomal to mitochondria signalling via lipid pools to enhance cellular mitochondrial function and organismal health.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tharyan, Rebecca George UNSPECIFIED UNSPECIFIED UNSPECIFIED Annibal, Andrea UNSPECIFIED orcid.org/0000-0003-4311-5417 UNSPECIFIED Schiffer, Isabelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Laboy, Raymond UNSPECIFIED orcid.org/0000-0002-0375-1550 UNSPECIFIED Atanassov, Ilian UNSPECIFIED orcid.org/0000-0001-8259-2545 UNSPECIFIED Weber, Anna Luise UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerisch, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Antebi, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-335213
DOI:	10.1038/s42255-020-0200-2
Journal or Publication Title:	Nat. Metab.
Volume:	2
Number:	5
Page Range:	S. 387 - 406
Date:	2020
Publisher:	NATURE RESEARCH
Place of Publication:	BERLIN
ISSN:	2522-5812
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CAENORHABDITIS-ELEGANS; LIFE-SPAN; NF-Y; STRESS; CARDIOLIPIN; QUANTIFICATION; BIOGENESIS; PATHWAYS; NUCLEAR; GENES Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33521