Transcription factor NFYB-1 regulates mitochondrial function and promotes longevity induced by mitochondrial impairment

Identification: Tharyan, Rebecca

Transcription factor NFYB-1 regulates mitochondrial function and promotes longevity induced by mitochondrial impairment
Tharyan, R1, Gerisch, B1, Antebi, A1, 2
1Max Planck Institute for Biology of Ageing, Cologne, Germany; 2Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Mitochondrial integrity is critical for cellular function and organismal life span, yet the underlying mechanisms linking mitochondrial function to other intracellular organelles and animal longevity is unclear. In this study, we addressed these questions in nematode C. elegans. Upon shift from food to no food prior to sexual maturation, C. elegans can enter an adult reproductive diapause (ARD), during which they undergo metabolic remodelling and can live months without food. C. elegans exit ARD when reintroduced to food. We found mitochondrial marker expression, number, morphology and respiration rate to be regulated under ARD entry and exit. Additionally, ARD longevity is impacted by mitochondrial fusion/fission factors. To identify novel loci involved in mitochondrial regulation, using ARD recovery as a tool we performed an RNAi screen monitoring expression of the mitochondrial marker pcco-1::gfp during ARD recovery. We identified presumed ancestral factors known to regulate mitochondrial function, including CREB, CREB binding protein, ATFS-1 and SKN-1.
More importantly we also found several novel mitochondrial regulators such as NFYB-1, a subunit of the NF-Y transcriptional complex binding the CCAAT motif. Consistent with a role in mitochondrial physiology, we observed that loss of NFYB-1 leads to mitochondrial fragmentation, reduced mitochondrial reporter expression, lower oxygen consumption and abolition of longevity triggered by reduced mitochondrial function by RNAi knockdown of cco-1 RNAi and mitochondrial mutant isp-1(qm150). Moreover, NFYB-1 loss also regulates mitochondrial to cytosolic stress response and localization of mitochondrial UPR factors ATFS-1 and DEV-1. Strikingly both proteomics and transcriptomics analysis indicates that NFYB-1 regulates a subset of endoplasmic reticulum associated genes. Taken together these findings suggest that NFYB-1 promotes mitochondrial gene expression, while suppressing ER stress response and functions as a novel regulator to maintain homeostasis and mitochondrial longevity.


Credits: None available.