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001-es BibID:BIBFORM095719
035-os BibID:(WoS)000668898600016
Első szerző:Shaw, Abhirup
Cím:Mitophagy is downregulated upon thermogenic stimulus in human beige adipocytes / Shaw Abhirup, Szatmári-Tóth Mária, Csomós István, Mocsár Gábor, Balajthy Zoltán, Győry Ferenc, Kristóf Endre Károly, Fésüs László
Dátum:2021
ISSN:2211-5463
Megjegyzések:Adipocytes are classi?ed into white, brown and beige. Brown and beige adipocytes are important targets to combat obesity, as they are capable to dissipate energy in the form of heat, while the white adipocytes are primarily for energy storage. UCP1, an inner mitochondrial membrane protein mediates thermogenesis by uncoupling the mitochondrial respiratory chain from ATP synthesis. Hence, mitochondria are important for the thermogenic and metabolic functions of adipocytes. UCP1+ mitochondria in human adipocytes are mostly fragmented (Pisani et al, 2017). Mitophagy plays a vital role in beige to white adipocyte transition in mouse (Altshuler-Keylin et al, 2016). We intend to characterize the role of mitophagy in the thermogenic activation of primary human abdominal subcutaneous adipocytes and SGBS cells. Isolated preadipocytes were differentiated into white and browning adipocytes, which were treated with dibutyryl-cAMP (6, 10 and 14 hours). Genes related to parkin-dependent and independent mitophagy were downregulated upon thermogenic stimulus; the parkin dependent ones being the most downregulated. The lipidated form of LC3, LC3-II is recruited on the outer membrane of the autophagosome which indicates ongoing autophagy. TOM20 is an outer mitochondrial membrane protein and marks the mitochondria. LC3 and TOM20 immunostaining were performed, followed by quanti?cation of LC3 punctae,which was high in untreated control adipocytes but decreased signi?cantly upon thermogenic stimulus, suggesting repressed autophagy/mitophagy. Colocalization of TOM20 and LC3 can indicate mitophagy. Decreased colocalization was observed upon thermogenic stimulus, which further proved repressed mitophagy.TOM20 quanti?cation showed increased number of fragmented mitochondria upon thermogenic stimulus suggesting prompt inhibition of mitophagy, thereby protecting many fragmented mitochondria from degradation and boosting thermogenesis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
folyóiratcikk
Megjelenés:FEBS Open Bio. - 11 : S1 (2021), p. 9. -
További szerzők:Szatmári-Tóth Mária (1987-) (molekuláris biológus) Csomós István (1983-) (molekuláris biológus) Mocsár Gábor (1981-) (biofizikus) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Győry Ferenc (1964-) (sebész) Kristóf Endre (1987-) (általános orvos) Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00006
GINOP
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Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:BIBFORM087859
035-os BibID:(cikkazonosító)6640 (scopus)85090621567 (wos)000580228400001
Első szerző:Szatmári-Tóth Mária (molekuláris biológus)
Cím:Thermogenic Activation Downregulates High Mitophagy Rate in Human Masked and Mature Beige Adipocytes / Mária Szatmári-Tóth, Abhirup Shaw, István Csomós, Gábor Mocsár, Pamela Fischer-Posovszky, Martin Wabitsch, Zoltán Balajthy, Cecília Lányi, Ferenc Győry, Endre Kristóf, László Fésüs
Dátum:2020
ISSN:1661-6596 1422-0067
Megjegyzések:Thermogenic brown and beige adipocytes oxidize metabolic substrates producing heat, mainly by the mitochondrial uncoupling protein UCP1, and can thus counteract obesity. Masked beige adipocytes possess white adipocyte-like morphology, but can be made thermogenic by adrenergic stimuli. We investigated the regulation of mitophagy upon thermogenic activation of human masked and mature beige adipocytes. Human primary abdominal subcutaneous adipose-derived stromal cells (hASCs) and SGBS preadipocytes were differentiated to white and beige adipocytes, then their cAMP-induced thermogenic potential was assessed by detecting increased expressions of UCP1, mitochondrial DNA content and respiratory chain complex subunits. cAMP increased the thermogenic potential of white adipocytes similarly to beige ones, indicating the presence of a masked beige population. In unstimulated conditions, a high autophagic flux and mitophagy rates (demonstrated by LC3 punctae and TOM20 co-immunostaining) were observed in white adipocytes, while these were lower in beige adipocytes. Silencing and gene expression experiments showed that the ongoing mitophagy was Parkin-independent. cAMP treatment led to the downregulation of mitophagy through PKA in both types of adipocytes, resulting in more fragmented mitochondria and increased UCP1 levels. Our data indicates that mitophagy is repressed upon encountering a short-term adrenergic stimulus, as a fast regulatory mechanism to provide high mitochondrial content for thermogenesis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:International Journal of Molecular Sciences. - 21 : 18 (2020), p. 1-21. -
További szerzők:Shaw, Abhirup (1992-) Csomós István (1983-) (molekuláris biológus) Mocsár Gábor (1981-) (biofizikus) Fischer-Posovszky Pamela Wabitsch, Martin Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Lányi Cecília Győry Ferenc (1964-) (sebész) Kristóf Endre (1987-) (általános orvos) Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00006
GINOP
FK131424
OTKA
K129139
OTKA
ÚNKP-20-5-DE-12
Egyéb
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
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