Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids DOI Creative Commons
Katharina Papsdorf, Jason W. Miklas,

Amir Hosseini

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(5), P. 672 - 684

Published: May 1, 2023

Abstract Dietary mono-unsaturated fatty acids (MUFAs) are linked to longevity in several species. But the mechanisms by which MUFAs extend lifespan remain unclear. Here we show that an organelle network involving lipid droplets and peroxisomes is critical for MUFA-induced Caenorhabditis elegans . upregulate number of fat storage tissues. Increased droplet necessary predicts remaining lifespan. Lipidomics datasets reveal also modify ratio membrane lipids ether lipids—a signature associated with decreased oxidation. In agreement this, decrease oxidation middle-aged individuals. Intriguingly, not only but peroxisome number. A targeted screen identifies genes involved co-regulation peroxisomes, reveals induction both organelles optimal longevity. Our study uncovers homeostasis regulation, opening new avenues interventions delay aging.

Language: Английский

HIF-1α drives resistance to ferroptosis in solid tumors by promoting lactate production and activating SLC1A1 DOI Creative Commons
Zhou Yang, Wei Su, Xiyi Wei

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(8), P. 112945 - 112945

Published: Aug. 1, 2023

Solid tumors have developed robust ferroptosis resistance. The mechanism underlying resistance regulation in solid tumors, however, remains elusive. Here, we report that the hypoxic tumor microenvironment potently promotes a hypoxia-inducible factor 1α (HIF-1α)-dependent manner. In combination with HIF-2α, which under hypoxia, HIF-1α is main driver of hypoxia-induced Mechanistically, HIF-1α-induced lactate contributes to pH-dependent manner parallel classical SLC7A11 and FSP1 systems. addition, also enhances transcription SLC1A1, an important glutamate transporter, cystine uptake promote support role hypoxia resistance, silencing sensitizes mouse inducers. conclusion, our results reveal by drives identify alleviation induction as promising therapeutic strategy for tumors.

Language: Английский

Citations

83
Lipid droplets and cellular lipid flux DOI

Alyssa J. Mathiowetz,

James A. Olzmann

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(3), P. 331 - 345

Published: March 1, 2024

Language: Английский

Citations

80
CDKN2A deletion remodels lipid metabolism to prime glioblastoma for ferroptosis DOI Creative Commons

Jenna K. Minami,

Danielle Morrow,

Nicholas Bayley

et al.

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(6), P. 1048 - 1060.e9

Published: May 25, 2023

Malignant tumors exhibit heterogeneous metabolic reprogramming, hindering the identification of translatable vulnerabilities for metabolism-targeted therapy. How molecular alterations in promote diversity and distinct targetable dependencies remains poorly defined. Here we create a resource consisting lipidomic, transcriptomic, genomic data from 156 molecularly diverse glioblastoma (GBM) derivative models. Through integrated analysis GBM lipidome with datasets, identify CDKN2A deletion remodels lipidome, notably redistributing oxidizable polyunsaturated fatty acids into lipid compartments. Consequently, CDKN2A-deleted GBMs display higher peroxidation, selectively priming ferroptosis. Together, this study presents lipidomic clinical preclinical specimens, which leverage to detect therapeutically exploitable link between recurring lesion altered metabolism GBM.

Language: Английский

Citations

79
Diet, lipids, and antitumor immunity DOI Creative Commons
Hannah Prendeville, Lydia Lynch

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(3), P. 432 - 444

Published: Jan. 5, 2022

Tumour growth and dissemination is largely dependent on nutrient availability. It has recently emerged that the tumour microenvironment rich in a diverse array of lipids increase abundance with progression play role promoting metastasis. Here, we describe pro-tumorigenic roles lipid uptake, metabolism synthesis detail therapeutic potential targeting cancer. Additionally, highlight new insights into distinct immunosuppressive effects microenvironment. Lipids threaten an anti-tumour environment whereby metabolic adaptation to linked immune dysfunction. Finally, differential commondietary cancer which may uncover for specific dietary regimens association traditional therapies. Understanding relationship between lipids, tumour, cells important context obesity reveal possibility harness diet treatment cancers.

Language: Английский

Citations

78
Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids DOI Creative Commons
Katharina Papsdorf, Jason W. Miklas,

Amir Hosseini

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(5), P. 672 - 684

Published: May 1, 2023

Abstract Dietary mono-unsaturated fatty acids (MUFAs) are linked to longevity in several species. But the mechanisms by which MUFAs extend lifespan remain unclear. Here we show that an organelle network involving lipid droplets and peroxisomes is critical for MUFA-induced Caenorhabditis elegans . upregulate number of fat storage tissues. Increased droplet necessary predicts remaining lifespan. Lipidomics datasets reveal also modify ratio membrane lipids ether lipids—a signature associated with decreased oxidation. In agreement this, decrease oxidation middle-aged individuals. Intriguingly, not only but peroxisome number. A targeted screen identifies genes involved co-regulation peroxisomes, reveals induction both organelles optimal longevity. Our study uncovers homeostasis regulation, opening new avenues interventions delay aging.

Language: Английский

Citations

74