Mony, V. K., Benjamin, S. & O’Rourke, E. J. A lysosome-centered view of nutrient homeostasis. Autophagy 12, 619–631 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu, G. Y. & Sabatini, D. M. mTOR at the nexus of nutrition, growth, ageing and disease. Nat. Rev. Mol. Cell Biol. 21, 183–203 (2020). A review discussing the intimate association between lysosomes and mTORC that is required to regulate cellular metabolic fate in states of nutrition or starvation in health and disease.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Platt, F. M., d’Azzo, A., Davidson, B. L., Neufeld, E. F. & Tifft, C. J. Lysosomal storage diseases. Nat. Rev. Dis. Primers 4, 27 (2018).

Article  PubMed  Google Scholar 

de Duve, C. The participation of lysosomes in the transformation of smooth muscle cells to foamy cells in the aorta of cholesterol-fed rabbits. Acta Cardiol. 20, 9–25 (1974). Recognition of atherosclerotic plaque as a form of LSD as a consequence of neutral lipid deposition in lysosomes of foam cells.

Google Scholar 

Bar-Peled, L. & Sabatini, D. M. Regulation of mTORC1 by amino acids. Trends Cell Biol. 24, 400–406 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Meng, Y., Heybrock, S., Neculai, D. & Saftig, P. Cholesterol handling in lysosomes and beyond. Trends Cell Biol. 30, 452–466 (2020).

Article  CAS  PubMed  Google Scholar 

Zhang, X. et al. High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy. Nat. Metab. 2, 110–125 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zernecke, A. et al. Meta-analysis of leukocyte diversity in atherosclerotic mouse aortas. Circ. Res. 127, 402–426 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chinetti-Gbaguidi, G., Colin, S. & Staels, B. Macrophage subsets in atherosclerosis. Nat. Rev. Cardiol. 12, 10–17 (2015).

Article  CAS  PubMed  Google Scholar 

Wculek, S. K., Dunphy, G., Heras-Murillo, I., Mastrangelo, A. & Sancho, D. Metabolism of tissue macrophages in homeostasis and pathology. Cell. Mol. Immunol. 19, 384–408 (2022).

Article  CAS  PubMed  Google Scholar 

O’Neill, L. A. J. & Artyomov, M. N. Itaconate: the poster child of metabolic reprogramming in macrophage function. Nat. Rev. Immunol. 19, 273–281 (2019).

Article  PubMed  Google Scholar 

West, A. P. et al. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 472, 476–480 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nomura, M. et al. Fatty acid oxidation in macrophage polarization. Nat. Immunol. 17, 216–217 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang, S. C. C. et al. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat. Immunol. 15, 846–855 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu, R. et al. Lipid-associated macrophages between aggravation and alleviation of metabolic diseases. Trends Endocrinol. Metab. https://doi.org/10.1016/j.tem.2024.04.009 (2024).

Jaitin, D. A. et al. Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner. Cell 178, 686–698.e14 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dib, L. et al. Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications. Nat. Cardiovasc. Res. 2, 656–672 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Viaud, M. et al. Lysosomal cholesterol hydrolysis couples efferocytosis to anti-inflammatory oxysterol production. Circ. Res. 122, 1369–1384 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jha, A. K. et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42, 419–430 (2015).

Article  CAS  PubMed  Google Scholar 

Tannahill, G. M. et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496, 238–242 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yan, C. et al. Macrophage-specific expression of human lysosomal acid lipase corrects inflammation and pathogenic phenotypes in lal−/− mice. Am. J. Pathol. 169, 916–926 (2006).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, F. et al. Hepatic lysosomal acid lipase drives the autophagy-lysosomal response and alleviates cholesterol metabolic disorder in ApoE deficient mice. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1866, 159027 (2021).

Article  CAS  PubMed  Google Scholar 

Schott, M. B. et al. Lipid droplet size directs lipolysis and lipophagy catabolism in hepatocytes. J. Cell Biol. 218, 3320–3335 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ouimet, M. et al. Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. Cell Metab. 13, 655–667 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tavakoli, S., Zamora, D., Ullevig, S. & Asmis, R. Bioenergetic profiles diverge during macrophage polarization: implications for the interpretation of 18F-FDG PET imaging of atherosclerosis. J. Nucl. Med. 54, 1661–1667 (2013).

Article  CAS  PubMed  Google Scholar 

Susser, L. I. et al. Mitochondrial fragmentation promotes inflammation resolution responses in macrophages via histone lactylation. Mol. Cell. Biol. 43, 531–546 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Afroz, S. F. et al. Mitochondrial dynamics in macrophages: divide to conquer or unite to survive? Biochem. Soc. Trans. 51, 41–56 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vergadi, E., Ieronymaki, E., Lyroni, K., Vaporidi, K. & Tsatsanis, C. Akt signaling pathway in macrophage activation and M1/M2 polarization. J. Immunol. 198, 1006–1014 (2017).

Article  CAS  PubMed  Google Scholar 

Huang, S. C. C. et al. Metabolic reprogramming mediated by the mTORC2–IRF4 signaling axis is essential for macrophage alternative activation. Immunity 45, 817–830 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T. & Castegna, A. The metabolic signature of macrophage responses. Front. Immunol. 10, 1462 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar