Rapamycin

high-resolution terminology - matching measurements at high-resolution

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

	Year	Reference	Organism	Tissue;cell
Brunetta 2019 J Funct Foods	2019	Brunetta 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.	Mouse	Skeletal muscle
Gabandé-Rodríguez 2019 Cells	2019	Gabandé-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.
Zhou 2018 Toxicology	2018	Zhou 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.	Rat	Other cell lines
Nacarelli 2018 Geroscience	2018	Nacarelli 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.	Human	Heart Fibroblast
Civiletto 2018 EMBO Mol Med	2018	Civiletto 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.	Mouse	Skeletal muscle
Seo 2017 Elife	2017	Seo 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 Biol	2017	Zhou 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.	Rat	Kidney
Yu 2017 Free Radic Biol Med	2017	Yu 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.	Mouse	Heart
Sivertsson 2017 Am J Physiol Renal Physiol	2017	Sivertsson 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.	Rat	Kidney
Reis 2016 Aging (Albany NY)	2016	Reis 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.	Mouse	Fat
Sundaram 2015 Mol Microbiol	2015	Sundaram 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 Science	2014	Cheng 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.	Human	Blood cells Other cell lines
Kim 2013 PLoS Genet	2013	Kim 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 Biol	2013	Sivertsson E, Friederich-Persson M (2013) Inhibition of mammalian target of rapamycin induces renal mitochondrial uncoupling in rats. Adv Exp Med Biol 789:309-14.	Rat	Kidney
Bratic 2013 J Clin Invest	2013	Bratic A, Larsson NG (2013) The role of mitochondria in aging. J Clin Invest 123:951-7.	Human Mouse Other mammals Drosophila Caenorhabditis elegans
Ye 2013 Aging	2013	Ye 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.	Mouse	Other cell lines Skeletal muscle
Dutta 2013 Autophagy	2013	Dutta 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.	Mouse	Heart

	Year	Reference	Organism	Tissue;cell
Alves 2018 MiPschool Tromso E2	2018	Role for mitochondria on the response of highly proliferative and invasive bladder cancer cells to the combined inhibition of mTOR and SIRT1.	Human	Endothelial;epithelial;mesothelial cell
Barriocanal-Casado 2015 Abstract MiP2015	2015	Targeting nutrient signaling pathways for the treatment of mitochondrial diseases.	Mouse
Fessel 2013 Abstract IOC75	2013	Fessel 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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Term	Abbreviation	Description
Aspirin		Aspirin is a widely applied drug that requires dosage adjusted to individual body mass. It is a non-selective COX inhibitor and exerts an effect on long-chain fatty acid transport into mitochondria.
Curcumin		Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. The protective effects of curcumin on rat heart mitochondrial injuries induced by in vitro anoxia–reoxygenation were evaluated by Xu et al 2013. It was found that curcumin added before anoxia or immediately prior to reoxygenation exhibited remarkable protective effects against anoxia–reoxygenation induced oxidative damage to mitochondria.
Elamipretide	Bendavia	Bendavia (Elamipretide) was developed as a mitochondria-targeted drug against degenerative diseases, including cardiac ischemia-reperfusion injury. Clinical trials showed variable results. It is a cationic tetrapeptide which readily passes cell membranes, associates with cardiolipin in the mitochondrial inner membrane. Supercomplex-associated CIV activity significantly improved in response to elamipretide treatment in the failing human heart.
Flavonoids		Flavonoids are a group of bioactive polyphenols with potential antioxidant and anti-inflammatory effects, abundant in fruits and vegetables, and in some medicinal herbs. Flavonoids are synthesized in plants from phenylalanine. Dietary intake of flavonoids as nutraceuticals is discussed for targeting T2D and other degenerative diseases.
Melatonin	aMT	Melatonin (N-acetyl-5-methoxytryptamine, aMT) is a highly conserved molecule present in unicellular to vertebrate organisms. Melatonin is synthesized from tryptophan in the pinealocytes by the pineal gland and also is produced in other organs, tissues and fluids (extrapineal melatonin). Melatonin has lipophilic and hydrophilic nature which allows it to cross biological membranes. Therefore, melatonin is present in all subcellular compartments predominantly in the nucleus and mitochondria. Melatonin has pleiotropic functions with powerful antioxidant, anti-inflammatory and oncostatic effects with a wide spectrum of action particularly at the level of mitochondria. » MiPNet article
Metformin		Metformin is mainly known as an important antidiabetic drug which is effective, however, in a wide spectrum of degenerative diseases. It is an inhibitor of Complex I and glycerophosphate dehydrogenase complex.
Rapamycin		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.
Resveratrol		Resveratrol is a natural bioactive phenol prouced by several plants with antioxidant and anti-inflammatory effects. Dietary intake as nutraceutical is discussed for targeting mitochondria with a wide spectrum of action in degenerative diseases.
Spermidine		Spermidine 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.

Healthy reference population

Body mass excess

BFE

BME cutoffs

BMI

H

M

VO2max

mitObesity drugs

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MitoPedia:mitObesity drug