Oda, A. | bioRxiv Science

bioRxiv2024

Loss of long-chain acyl-CoA dehydrogenase protects against acute kidney injury

Proximal tubular epithelial cells (PTECs) are particularly vulnerable to acute kidney injury (AKI). While fatty acids are the preferred energy source for PTECs via fatty acid oxidation (FAO), FAO-mediated H2O2 production in mitochondria has been shown to be a major source of oxidative stress. We have previously shown that a mitochondrial flavoprotein, long-chain acyl-CoA dehydrogenase (LCAD), which catalyzes a key step in mitochondrial FAO, directly produces H2O2 in vitro. Further we have established that loss of a lysine deacylase, Sirtuin 5 (Sirt5-/-), induces hypersuccinylation and inhibition of mitochondrial FAO genes to stimulate peroxisomal FAO and to protect against AKI. However, the role of LCAD has yet to be determined. Mass spectrometry data acquisition revealed that LCAD is hypersuccinylated in Sirt5-/- kidneys after AKI. Following two distinct models of AKI, cisplatin treatment or renal ischemia/reperfusion (IRI), LCAD knockout mice (LCAD-/-) demonstrated renoprotection against AKI. Specifically, LCAD-/- kidneys displayed mitigated renal tubular injury, decreased oxidative stress, preserved mitochondrial function, enhanced peroxisomal FAO, and decreased ferroptotic cell death. LCAD deficiency confers protection against two distinct models of AKI. This suggests a therapeutically attractive mechanism whereby preserved mitochondrial respiration as well as enhanced peroxisomal FAO by loss of LCAD mediates renoprotection against AKI.

pathology↗

bioRxiv2017

Transcriptomes and Raman spectra are linked linearly through a shared low-dimensional subspace

Raman spectroscopy is an imaging technique that can reflect whole-cell molecular compositions in vivo, and has been applied recently in cell biology to characterize different cell types and states. However, due to the complex molecular compositions and spectral overlaps, the interpretation of cellular Raman spectra have remained unclear. In this report, we compared cellular Raman spectra to transcriptomes of Schizosaccharomyces pombe and Escherichia coli, and provide firm evidence that they can be computationally connected and interpreted. Specifically, we find that the dimensions of high-dimensional Raman spectra and transcriptomes measured by RNA-seq can be effectively reduced and connected linearly through a shared low-dimensional subspace. Accordingly, we were able to reconstruct global gene expression profiles by applying the calculated transformation matrix to Raman spectra, and vice versa. Strikingly, highly expressed ncRNAs contributed to the Raman-transcriptome linear correspondence more significantly than mRNAs in S. pombe, which implies their major role in coordinating molecular compositions. This compatibility between whole-cell Raman spectra and transcriptomes marks an important and promising step towards establishing spectroscopic live-cell omics studies.

systems biology↗