Disruption of the TCA cycle reveals an ATF4-mediated integration of redox and amino acid metabolism

The Tricarboxylic Acid (TCA) cycle is arguably the most critical metabolic
cycle in physiology and exists as an essential interface coordinating
cellular metabolism, bioenergetics, and redox homeostasis. Despite decades
of research, a comprehensive investigation into the consequences of TCA
cycle dysfunction remains elusive. Here, we targeted two TCA cycle
enzymes, fumarate hydratase (FH), using an FH inhibitor (FHIN-1), and
succinate dehydrogenase (SDH), using two inhibitors Atpenin A5 (AA5) and
thenoyltrifluoroacetone (TTFA), and combined transcriptomics, and
proteomics analyses to fully appraise the consequences of TCA cycle
inhibition (TCAi) in murine kidney epithelial cell line. Data from this
study that is included in this Dryad submission is as follows: 1. TruSeq
mRNA stranded analysis of murine Fh1fl/fl kidney epithelial cells
were treated with vehicle control (DMSO) or 20 micromolar fumarate
hydratase inhibitor (FHIN-1) for 24 h. Three biological replicates per
condition.  2. TruSeq mRNA stranded analysis of murine
Fh1fl/fl kidney epithelial cells treated with vehicle
control (DMSO) or Atpenin A5 (AA5) for 24 h. Three biological
replicates per condition.  3. Label-free proteomic analysis of a
murine Fh1fl/fl kidney epithelial cells treated with
vehicle control (DMSO) or 20 micromolar FHIN-1 for 24 h.
Five biological replicates per condition.  4. Label-free
proteomic analysis of a murine Fh1fl/fl kidney epithelial cells
treated with vehicle control (DMSO) and 500 micromolar
thenoyltrifluoroacetone (TTFA). Five biological replicates per
condition.  5. Western blot uncropped blots