Rapamycin

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Rapamycin

Description

Rapamycin is an inhibitor of the mammalian/mechanistic target of rapamycin, complex 1 (mTORC1). Rapamycin induces autophagy and dyscouples mitochondrial respiration. Rapamycin delays senescence in human cells, and extends lifespan in mice without detrimental effects on mitochondrial fitness in skeletal muscle.


Reference: Ye 2013 Aging

Rapamycin and mitObesity

Work in progress by Gnaiger E 2020-02-23 linked to a preprint in preparation on BME and mitObesity.

References: Rapamycin

 YearReferenceOrganismTissue;cell
Gabandé-Rodríguez 2019 Cells2019Gabandé-Rodríguez E, M Gómez de Las Heras M, Mittelbrunn M (2019) Control of inflammation by calorie restriction mimetics: on the crossroad of autophagy and mitochondria. Cells 2019;9:E82.
Brunetta 2019 J Funct Foods2019Brunetta HS, de Paula GC, Fritzen M, Cecchini MS, dos Santos GJ, Nazari EM, Rafacho A, de Bem AF, Nunes EA (2019) Leucine increases muscle mitochondrial respiration and attenuates glucose intolerance in diet-induced obesity in Swiss mice. J Funct Foods 62:103544.MouseSkeletal muscle
Zhou 2018 Toxicology2018Zhou Q, Fu X, Wang X, Wu Q, Lu Y, Shi J, Klaunig JE, Zhou S (2018) Autophagy plays a protective role in Mn-induced toxicity in PC12 cells. Toxicology 394:45–53.RatOther cell lines
Nacarelli 2018 Geroscience2018Nacarelli T, Azar A, Altinok O, Orynbayeva Z, Sell C (2018) Rapamycin increases oxidative metabolism and enhances metabolic flexibility in human cardiac fibroblasts. Geroscience 40:243-56.HumanHeart
Fibroblast
Civiletto 2018 EMBO Mol Med2018Civiletto G, Dogan SA, Cerutti R, Fagiolari G, Moggio M, Lamperti C, Benincá C, Viscomi C, Zeviani M (2018) Rapamycin rescues mitochondrial myopathy via coordinated activation of autophagy and lysosomal biogenesis. EMBO Mol Med 10:e8799.MouseSkeletal muscle
Sivertsson 2017 Am J Physiol Renal Physiol2017Sivertsson E, Friederich-Persson M, Öberg CM, Fasching A, Hansell P, Rippe B, Palm F (2017) Inhibition of mammalian target of rapamycin decreases intrarenal oxygen availability and alters glomerular permeability. Am J Physiol Renal Physiol 314:F864-F872.RatKidney
Seo 2017 Elife2017Seo AY, Lau PW, Feliciano D, Sengupta P, Gros MAL, Cinquin B, Larabell CA, Lippincott-Schwartz J (2017) AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation. Elife 6. pii: e21690.Saccharomyces cerevisiae
Zhou 2017 Int J Biochem Mol Biol2017Zhou Q, Zhang H, Wu Q, Shi J, Zhou S (2017) Pharmacological manipulations of autophagy modulate paraquat-induced cytotoxicity in PC12 cells. Int J Biochem Mol Biol 8:13-22.RatKidney
Yu 2017 Free Radic Biol Med2017Yu Y, Wang L, Delguste F, Durand A, Guilbaud A, Rousselin C, Schmidt AM, Tessier F, Boulanger E, Neviere R (2017) Advanced glycation end products receptor RAGE controls myocardial dysfunction and oxidative stress in high-fat fed mice by sustaining mitochondrial dynamics and autophagy-lysosome pathway. Free Radic Biol Med 112:397-410.MouseHeart
Reis 2016 Aging (Albany NY)2016Reis FC, Branquinho JL, Brandão BB, Guerra BA, Silva ID, Frontini A, Thomou T, Sartini L, Cinti S, Kahn CR, Festuccia WT, Kowaltowski AJ, Mori MA (2016) Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice. Aging (Albany NY) 8:1201-22.MouseFat
Sundaram 2015 Mol Microbiol2015Sundaram V, Petkova MI, Pujol-Carrion N, Boada J, de la Torre-Ruiz MA (2015) Tor1, Sch9 and PKA downregulation in quiescence rely on Mtl1 to preserve mitochondrial integrity and cell survival. Mol Microbiol 97:93-109.Saccharomyces cerevisiae
Cheng 2014 Science2014Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, Giamarellos-Bourboulis EJ, Martens JH, Rao NA, Aghajanirefah A, Manjeri GR6, Li Y, Ifrim DC, Arts RJ, van der Meer BM, Deen PM, Logie C, O'Neill LA, Willems P, van de Veerdonk FL, van der Meer JW, Ng A, Joosten LA, Wijmenga C, Stunnenberg HG, Xavier RJ, Netea MG (2014) mTOR- and HIF-1 α–mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345:1250684.HumanBlood cells
Other cell lines
Ye 2013 Aging2013Ye L, Widlund AL, Sims CA, Lamming DW, Guan Y, Davis JG, Sabatini DM, Harrison DE, Vang O, Baur JA (2013) Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance. Aging (Albany NY) 5:539-50.MouseOther cell lines
Skeletal muscle
Dutta 2013 Autophagy2013Dutta D, Xu J, Kim J-S, Dunn WA Jr, Leeuwenburgh C (2013) Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity. Autophagy 9:328-44.MouseHeart
Kim 2013 PLoS Genet2013Kim S-H, Scott SA, Bennett MJ, Carson RP, Fessel JP, Brown HA, Ess KC (2013) Multi-organ abnormalities and mTORC1 activation in zebrafish model of multiple acyl-CoA dehydrogenase deficiency. PLoS Genet 9:e1003563.Zebrafish
Fishes
Sivertsson 2013 Adv Exp Med Biol2013Sivertsson E, Friederich-Persson M (2013) Inhibition of mammalian target of rapamycin induces renal mitochondrial uncoupling in rats. Adv Exp Med Biol 789:309-14.RatKidney
Bratic 2013 J Clin Invest2013Bratic A, Larsson NG (2013) The role of mitochondria in aging. J Clin Invest 123:951-7.Human
Mouse
Other mammals
Drosophila
Caenorhabditis elegans
 YearReferenceOrganismTissue;cell
Alves 2018 MiPschool Tromso E22018
MiPsociety
Role for mitochondria on the response of highly proliferative and invasive bladder cancer cells to the combined inhibition of mTOR and SIRT1.
HumanEndothelial;epithelial;mesothelial cell
Barriocanal-Casado 2015 Abstract MiP20152015Targeting nutrient signaling pathways for the treatment of mitochondrial diseases.Mouse
Fessel 2013 Abstract IOC752013Fessel JP (2013) Structural, functional, and signaling abnormalities in mitochondria and multiple organ systems in a novel zebrafish model of multiple Acyl-CoA dehydrogenase deficiency (MADD). Mitochondr Physiol Network 18.03.

MitoPedia: mitObesity drugs

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TermAbbreviationDescription
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SpermidineSpermidine is a polycationic bioactive polyamine mainly found in wheat germ, soybean and various vegetables, involved in the regulation of mitophagy, cell growth and cell death. Like other caloric restriction mimetics, spermidine is effective in cardioprotection, neuroprotection and anticancer immunosuppression by preserving mitochondrial function and control of autophagy.
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