Matches in SemOpenAlex for { <https://semopenalex.org/work/W2963804962> ?p ?o ?g. }
- W2963804962 endingPage "3400" @default.
- W2963804962 startingPage "3387" @default.
- W2963804962 abstract "Fibroblasts from patients with Tangier disease carrying ATP-binding cassette A1 (ABCA1) loss-of-function mutations are characterized by cardiolipin accumulation, a mitochondrial-specific phospholipid. Suppression of ABCA1 expression occurs in glomeruli from patients with diabetic kidney disease (DKD) and in human podocytes exposed to DKD sera collected prior to the development of DKD. We demonstrated that siRNA ABCA1 knockdown in podocytes led to reduced oxygen consumption capabilities associated with alterations in the oxidative phosphorylation (OXPHOS) complexes and with cardiolipin accumulation. Podocyte-specific deletion of Abca1 (Abca1fl/fl) rendered mice susceptible to DKD, and pharmacological induction of ABCA1 improved established DKD. This was not mediated by free cholesterol, as genetic deletion of sterol-o-acyltransferase-1 (SOAT1) in Abca1fl/fl mice was sufficient to cause free cholesterol accumulation but did not cause glomerular injury. Instead, cardiolipin mediates ABCA1-dependent susceptibility to podocyte injury, as inhibition of cardiolipin peroxidation with elamipretide improved DKD in vivo and prevented ABCA1-dependent podocyte injury in vitro and in vivo. Collectively, we describe a pathway definitively linking ABCA1 deficiency to cardiolipin-driven mitochondrial dysfunction. We demonstrated that this pathway is relevant to DKD and that ABCA1 inducers or inhibitors of cardiolipin peroxidation may each represent therapeutic strategies for the treatment of established DKD." @default.
- W2963804962 created "2019-07-30" @default.
- W2963804962 creator A5001040509 @default.
- W2963804962 creator A5009683565 @default.
- W2963804962 creator A5012183480 @default.
- W2963804962 creator A5018962385 @default.
- W2963804962 creator A5020121906 @default.
- W2963804962 creator A5021600258 @default.
- W2963804962 creator A5028984753 @default.
- W2963804962 creator A5035573141 @default.
- W2963804962 creator A5038961698 @default.
- W2963804962 creator A5039510768 @default.
- W2963804962 creator A5041192532 @default.
- W2963804962 creator A5052727162 @default.
- W2963804962 creator A5052937412 @default.
- W2963804962 creator A5057733880 @default.
- W2963804962 creator A5065478151 @default.
- W2963804962 creator A5069972418 @default.
- W2963804962 creator A5071179920 @default.
- W2963804962 creator A5072573381 @default.
- W2963804962 creator A5073141203 @default.
- W2963804962 creator A5078381271 @default.
- W2963804962 creator A5079487840 @default.
- W2963804962 creator A5085959437 @default.
- W2963804962 creator A5087249159 @default.
- W2963804962 creator A5088560891 @default.
- W2963804962 creator A5091731877 @default.
- W2963804962 date "2019-07-22" @default.
- W2963804962 modified "2023-10-14" @default.
- W2963804962 title "ATP-binding cassette A1 deficiency causes cardiolipin-driven mitochondrial dysfunction in podocytes" @default.
- W2963804962 cites W1524519685 @default.
- W2963804962 cites W1555206873 @default.
- W2963804962 cites W1568406795 @default.
- W2963804962 cites W1607399348 @default.
- W2963804962 cites W1722845210 @default.
- W2963804962 cites W1860908381 @default.
- W2963804962 cites W1967057928 @default.
- W2963804962 cites W1970607230 @default.
- W2963804962 cites W1970660374 @default.
- W2963804962 cites W1972476228 @default.
- W2963804962 cites W1974184735 @default.
- W2963804962 cites W1986248905 @default.
- W2963804962 cites W1992565781 @default.
- W2963804962 cites W2009651121 @default.
- W2963804962 cites W2015643261 @default.
- W2963804962 cites W2017284901 @default.
- W2963804962 cites W2018490812 @default.
- W2963804962 cites W2028945502 @default.
- W2963804962 cites W2032950904 @default.
- W2963804962 cites W2046493105 @default.
- W2963804962 cites W2048177923 @default.
- W2963804962 cites W2050622384 @default.
- W2963804962 cites W2051227378 @default.
- W2963804962 cites W2051633984 @default.
- W2963804962 cites W2052118720 @default.
- W2963804962 cites W2052401089 @default.
- W2963804962 cites W2062730505 @default.
- W2963804962 cites W2062897750 @default.
- W2963804962 cites W2063942799 @default.
- W2963804962 cites W2075837574 @default.
- W2963804962 cites W2078598822 @default.
- W2963804962 cites W2081467822 @default.
- W2963804962 cites W2087234888 @default.
- W2963804962 cites W2091754751 @default.
- W2963804962 cites W2094077779 @default.
- W2963804962 cites W2097339389 @default.
- W2963804962 cites W2102235083 @default.
- W2963804962 cites W2105518486 @default.
- W2963804962 cites W2107221695 @default.
- W2963804962 cites W2108822380 @default.
- W2963804962 cites W2109691722 @default.
- W2963804962 cites W2114991593 @default.
- W2963804962 cites W2116729573 @default.
- W2963804962 cites W2117911689 @default.
- W2963804962 cites W2122028337 @default.
- W2963804962 cites W2137927119 @default.
- W2963804962 cites W2148718682 @default.
- W2963804962 cites W2150438639 @default.
- W2963804962 cites W2159639597 @default.
- W2963804962 cites W2161080023 @default.
- W2963804962 cites W2167729033 @default.
- W2963804962 cites W2168287443 @default.
- W2963804962 cites W2170213886 @default.
- W2963804962 cites W2170449776 @default.
- W2963804962 cites W2171031572 @default.
- W2963804962 cites W2285846084 @default.
- W2963804962 cites W2478556254 @default.
- W2963804962 cites W2536321822 @default.
- W2963804962 cites W2557595461 @default.
- W2963804962 cites W2566717232 @default.
- W2963804962 cites W2587878218 @default.
- W2963804962 cites W2630014874 @default.
- W2963804962 cites W2738066655 @default.
- W2963804962 cites W2768776000 @default.
- W2963804962 cites W2788432017 @default.
- W2963804962 cites W2794972088 @default.
- W2963804962 cites W2798146738 @default.
- W2963804962 cites W4252905168 @default.