Dataset Information

NFYB-1 regulates mitochondrial function and longevity via lysosomal prosaposin

ABSTRACT: Mitochondrial activity is critical for cellular vitality and organismal longevity, yet underlying regulatory mechanisms spanning these different levels of organization remain elusive. From RNAi screens for mitochondrial biogenesis, we discovered NFYB-1, a subunit of the NF-Y transcriptional complex, as an ancestral regulator of mitochondrial function. NFYB-1 loss leads to reduced mitochondrial gene expression and oxygen consumption, mitochondrial fragmentation, disruption of mitochondrial stress pathways, and abolition of organismal longevity triggered by mitochondrial impairment. Multi-omics analysis reveals that NFYB-1 is a potent repressor of the ER stress response, as well as lysosomal prosaposin. Surprisingly, limiting prosaposin expression alters ceramide and cardiolipin pools, restores mitochondrial fusion, gene expression and longevity. Thus, the NFYB-1/prosaposin axis coordinates lysosomal to mitochondrial communication to enhance cellular mitochondrial function and organismal health.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: Ilian Atanassov

LAB HEAD: Adam Antebi

PROVIDER: PXD013233 | Pride | 2020-03-11

REPOSITORIES: Pride

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			Action	DRS
	170803_QE_IA_AA_RT_01_03.raw	Raw
	170803_QE_IA_AA_RT_02_02.raw	Raw
	170803_QE_IA_AA_RT_03_02.raw	Raw
	170803_QE_IA_AA_RT_04_02.raw	Raw
	170803_QE_IA_AA_RT_05_02.raw	Raw

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NFYB-1 regulates mitochondrial function and longevity via lysosomal prosaposin.

Tharyan Rebecca George RG Annibal Andrea A Schiffer Isabelle I Laboy Raymond R Atanassov Ilian I Weber Anna Luise AL Gerisch Birgit B Antebi Adam A

Nature metabolism 20200518 5

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<sup>1-5</sup>. Here we show that Caenorhabditis elegans nuclear transcription factor Y, beta subunit (NFYB-1), a subunit of the NF-Y transcriptional complex<sup>6-8</sup>, is a crucial regulator of mitochondrial function. Identified in RNA interference (RNAi) screens, NFYB-1 l ...[more]

PMID: 32694663

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