![]() LC-MS/MS analysis showed that HSC70 and/or HSP90 are bound to HA-SLC4A11–transfected PS120 fibroblast whole-cell lysates or isolated mitochondria, suggesting trafficking through the chaperone-mediated carrier pathway. SLC4A11 does not contain canonical N-terminal mitochondrial targeting sequences. Knockdown or pharmacologic inhibition of chaperones in human corneal endothelial cells (HCECs) or mouse corneal endothelial cells (MCECs), ex vivo kidney, or HA-SLC4A11–transfected fibroblasts was performed to investigate the functional consequences of interfering with mitochondrial SLC4A11 trafficking. Direct protein interactions between SLC4A11 and chaperones were examined using coimmunoprecipitation analysis and proximity ligation assay. Thiol crosslinked peptide binding to SLC4A11 was screened by untargeted liquid chromatography/tandem mass spectrometry (LC-MS/MS) analysis. The presence of mitochondrial targeting sequences was examined using in silico mitochondrial proteomic analyses. However, the underlying mechanism of SLC4A11 targeting to mitochondria is unknown. ![]() SLC4A11, an electrogenic H + transporter, is found in the plasma membrane and mitochondria of corneal endothelium.
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