Thomas D. Jackson
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View article: Riboflavin drives nucleotide biosynthesis and iron-sulfur metabolism to promote acute myeloid leukemia
Riboflavin drives nucleotide biosynthesis and iron-sulfur metabolism to promote acute myeloid leukemia Open
Riboflavin is a diet-derived vitamin in higher organisms that serves as a precursor for flavin mononucleotide and flavin adenine dinucleotide, key cofactors that participate in oxidoreductase reactions. Here, using proteomic, metabolomic a…
View article: Riboflavin Drives Nucleotide Biosynthesis and Iron-Sulfur Metabolism to Promote Acute Myeloid Leukemia
Riboflavin Drives Nucleotide Biosynthesis and Iron-Sulfur Metabolism to Promote Acute Myeloid Leukemia Open
Cofactors, many of which are vitamin-derived, are organic molecules with diverse biological functions. They are required for many metabolic pathways and enzymatic reactions, and thus can influence cell proliferation and differentiation. Th…
View article: A chaperone-assisted mechanism of outer mitochondrial membrane TOM70 insertion protective against diet-induced obesity
A chaperone-assisted mechanism of outer mitochondrial membrane TOM70 insertion protective against diet-induced obesity Open
Outer mitochondrial membrane (OMM) proteins communicate with the cytosol and other organelles including the endoplasmic reticulum (ER)1,2. This communication is important in thermogenic adipocytes to increase energy expenditure that contro…
View article: Reduced Protein Import via TIM23 SORT Drives Disease Pathology in TIMM50-Associated Mitochondrial Disease
Reduced Protein Import via TIM23 SORT Drives Disease Pathology in TIMM50-Associated Mitochondrial Disease Open
TIMM50 is a core subunit of the TIM23 complex, the mitochondrial inner membrane translocase responsible for the import of pre-sequence-containing precursors into the mitochondrial matrix and inner membrane. Here we describe a mitochondrial…
View article: Selective Mitochondrial Respiratory Complex I Subunit Deficiency Causes Tumor Immunogenicity
Selective Mitochondrial Respiratory Complex I Subunit Deficiency Causes Tumor Immunogenicity Open
Targeting of specific metabolic pathways in tumor cells has the potential to sensitize them to immune-mediated attack. Here we provide evidence for a specific means of mitochondrial respiratory Complex I (CI) inhibition that improves tumor…
View article: Caspase-2 protects against ferroptotic cell death
Caspase-2 protects against ferroptotic cell death Open
Caspase-2, one of the most evolutionarily conserved member of the caspase family, is an important regulator of the cellular response to oxidative stress. Given that ferroptosis is suppressed by antioxidant defense pathways, such as that in…
View article: Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction
Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction Open
The mechanism of action of eprenetapopt (APR-246, PRIMA-1 MET ) as an anticancer agent remains unresolved, although the clinical development of eprenetapopt focuses on its reported mechanism of action as a mutant-p53 reactivator. Using unb…
View article: Sideroflexin 4 is a complex I assembly factor that interacts with the MCIA complex and is required for the assembly of the ND2 module
Sideroflexin 4 is a complex I assembly factor that interacts with the MCIA complex and is required for the assembly of the ND2 module Open
Significance Mitochondria are double-membraned eukaryotic organelles that house the proteins required for generation of ATP, the energy currency of cells. ATP generation within mitochondria is performed by five multisubunit complexes (comp…
View article: The TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism
The TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism Open
Proteomic profiling of Sengers patient fibroblasts and AGK knockout models identifies remodeling of the mitochondrial proteome, including mitochondrial one-carbon metabolism enzymes, inner membrane serine transporters, sideroflexins, and C…
View article: Genome-wide CRISPR screens reveal APR-246 (Eprenetapopt) triggers ferroptosis and inhibits iron-sulfur cluster biogenesis
Genome-wide CRISPR screens reveal APR-246 (Eprenetapopt) triggers ferroptosis and inhibits iron-sulfur cluster biogenesis Open
The mechanisms by which cells respond and adapt to oxidative stress are largely unknown but are key to developing a rationale for cancer therapies that target antioxidant pathways. APR-246 is a mutant-p53 targeted therapeutic currently und…
View article: The TIM22 complex regulates mitochondrial one-carbon metabolism by mediating the import of Sideroflexins
The TIM22 complex regulates mitochondrial one-carbon metabolism by mediating the import of Sideroflexins Open
The Acylglycerol Kinase (AGK) is a mitochondrial lipid kinase that contributes to protein biogenesis as a subunit of the TIM22 complex at the inner mitochondrial membrane. Mutations in AGK cause Sengers syndrome, an autosomal recessive con…
View article: Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjærg syndrome
Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjærg syndrome Open
Human Tim8a and Tim8b are members of an intermembrane space chaperone network, known as the small TIM family. Mutations in TIMM8A cause a neurodegenerative disease, Mohr-Tranebjærg syndrome (MTS), which is characterised by sensorineural he…
View article: Mitochondria—hubs for regulating cellular biochemistry: emerging concepts and networks
Mitochondria—hubs for regulating cellular biochemistry: emerging concepts and networks Open
Mitochondria are iconic structures in biochemistry and cell biology, traditionally referred to as the powerhouse of the cell due to a central role in energy production. However, modern-day mitochondria are recognized as key players in euka…