| 2013 |
TRIAP1 (p53CSV) forms a complex with PRELI in the mitochondrial intermembrane space (IMS) that exerts lipid transfer activity in vitro, supplying phosphatidic acid (PA) for cardiolipin (CL) synthesis in the inner membrane. Loss of TRIAP1 or PRELI impairs CL accumulation, facilitates cytochrome c release, and renders cells vulnerable to apoptosis; survival is rescued by exogenous phosphatidylglycerol. |
Co-immunoprecipitation, in vitro lipid transfer assay, loss-of-function (siRNA/KO) with cytochrome c release and apoptosis readouts, lipid rescue experiment |
Cell metabolism |
High |
23931759
|
| 2010 |
Mdm35 (the yeast ortholog of TRIAP1) binds Ups1 and Ups2 (PRELI-family proteins) in the mitochondrial IMS, protecting them from proteolytic degradation by Yme1 and Atp23 and ensuring their import, thereby regulating cardiolipin and phosphatidylethanolamine levels in mitochondrial membranes. |
Yeast genetics, co-immunoprecipitation, protease-sensitivity assays, deletion mutants with lipid quantification |
The EMBO journal |
High |
20657548
|
| 2016 |
Ups2-Mdm35 complexes (SLMO2-TRIAP1 in humans) function as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial IMS, enabling PS decarboxylation to phosphatidylethanolamine (PE) by Psd1 at the inner membrane; a recombinant Ups2-Mdm35 fusion protein exhibits PS transfer activity between liposomes in vitro. |
In vitro liposome lipid transfer assay with recombinant fusion protein, yeast null mutants with radiolabeled PS-to-PE conversion, genetic analysis |
The Journal of cell biology |
High |
27241913 27354379
|
| 2015 |
Crystal structure of the Ups1-Mdm35-PA complex (yeast ortholog of TRIAP1-PRELI) reveals that Ups1 forms a barrel-like structure with a tunnel-like PA-binding pocket covered by helix α2, while Mdm35 adopts a three-helical clamp-like structure wrapping around Ups1. Hydrophobic residues lining the pocket and helix α2, plus a hydrophilic surface patch near the PA phosphate-binding site, are critical for PA binding and transfer as shown by mutagenesis. |
X-ray crystallography, site-directed mutagenesis, in vitro PA-binding and transfer assays |
EMBO reports |
High |
26071601
|
| 2005 |
TRIAP1 (p53CSV) is a p53 target gene containing a p53-binding site in its second exon. Overexpression protects cells from DNA-damage-induced apoptosis, while siRNA knockdown enhances apoptosis. TRIAP1 interacts with Hsp70 in the cytoplasm, likely inhibiting apoptosome formation via Apaf-1. |
siRNA knockdown, overexpression, apoptosis assays, co-immunoprecipitation with Hsp70, reporter/binding-site analysis |
Cancer research |
Medium |
15735003
|
| 2013 |
A genome-wide genetic screen identified TRIAP1 as a specific repressor of p21 (CDKN1A) expression upon p53 activation; TRIAP1 depletion slows cell-cycle progression without broadly affecting PUMA-mediated apoptosis, placing TRIAP1 as a pathway-specific coregulator of the p53 transcriptional program. |
Genome-wide RNAi screen, targeted siRNA depletion, p21/PUMA expression readouts, cell-cycle analysis |
Cell reports |
Medium |
23684607
|
| 2016 |
TRIAP1 knockdown in NPC cells induces mitochondrial fragmentation, membrane potential alteration, and cytochrome c release from mitochondria into the cytosol, enhancing apoptosis; these effects are phenocopied by miR-320b overexpression and reversed by TRIAP1 restoration. |
siRNA knockdown, overexpression rescue, mitochondrial morphology imaging, membrane potential assay, cytochrome c fractionation, in vivo xenograft |
PLoS genetics |
Medium |
27428374
|
| 2015 |
TRIAP1 inhibits caspase-9 activation in the cytoplasm (apoptosome-blocking activity); stable overexpression of TRIAP1 in breast cancer cells increases doxorubicin-resistant clone formation, while siRNA knockdown of TRIAP1 in drug-resistant cells impairs growth in the presence of doxorubicin. |
Stable transfection/overexpression, siRNA, caspase-9 activity assay, colony formation under drug selection |
Oncology reports |
Medium |
25998939
|
| 2016 |
Stable shRNA-mediated silencing of TRIAP1 in RPMI8226 multiple myeloma cells increases late apoptosis accompanied by upregulation of APAF1 and caspase-9 expression, and activation of caspase-9 and caspase-3/7, establishing that TRIAP1 suppresses the APAF1/caspase-9 apoptosome pathway. |
Lentiviral shRNA stable knockdown, flow cytometry (annexin V/PI), qRT-PCR for APAF1 and caspase-9, caspase activity assays |
Biochimica et biophysica acta |
Medium |
27032384
|
| 2025 |
TRIAP1 is imported into the mitochondrial IMS via the MIA40 oxidative folding relay. In its reduced cytosolic state, TRIAP1 rapidly forms a hydrophobic, alpha-helical, marginally stable molten globule intermediate that biases oxidative folding toward a non-native Cys37-Cys47 kinetic trap. MIA40 accelerates TRIAP1 folding by 30-fold by driving oxidation of the inner disulfide bond (Cys18-Cys37) and then the outer disulfide bond (Cys8-Cys47), yielding the native two-disulfide-bridged structure and bypassing the kinetic trap. |
NMR, biochemical oxidative folding assays, disulfide-bond mapping, mutagenesis, in vitro MIA40 interaction assays |
The Journal of biological chemistry |
High |
39909379
|
| 2023 |
TRIAP1 upregulation in human cells after nocodazole treatment retains cytochrome c in mitochondria, opposing partial caspase activation caused by prolonged mitotic arrest, thereby enabling escape from the G1 arrest that follows mitotic slippage. Decreasing TRIAP1 re-sensitizes cells to nocodazole. |
Long-term cell-fate tracking, cytochrome c localization (mitochondrial fractionation/imaging), caspase activation assays, siRNA knockdown and overexpression, proliferation assays |
Cell reports |
Medium |
36917609
|
| 2023 |
Exercise training downregulates CHCHD4, a mitochondrial disulfide relay carrier, which decreases import of TRIAP1 into mitochondria. Reduced mitochondrial TRIAP1 lowers cardiolipin levels and promotes VDAC oligomerization in skeletal muscle, facilitating mtDNA release and activating cGAS-STING/NFKB innate immune signaling, ultimately downregulating MyoD and promoting oxidative slow-twitch fiber formation. |
Mouse genetic model (CHCHD4 haploinsufficiency), cardiolipin quantification, VDAC oligomerization assay, mtDNA release assay, cGAS-STING/NFKB pathway analysis, skeletal muscle fiber-type characterization |
Cell reports |
Medium |
38157298
|
| 2025 |
SLMO2 (PRELI) interacts with TRIAP1 in ovarian cancer cells, enhancing mitochondrial membrane potential, reducing ROS, and inhibiting autophagy-dependent apoptosis. Co-expression of SLMO2 and TRIAP1 promotes tumor cell growth in vivo. |
Co-immunoprecipitation/interaction assay, flow cytometry, western blotting for autophagy markers, mitochondrial membrane potential assay, ROS measurement, xenograft mouse model |
Histology and histopathology |
Medium |
40654025
|
| 2022 |
In colorectal cancer cells, TRIAP1 depletion perturbs mitochondrial ultrastructure and alters endoplasmic reticulum-dependent lipid homeostasis without a major impact on cardiolipin levels or mitochondrial respiratory activity. TRIAP1 depletion also induces a p53-mediated stress response and confers resistance to glutamine deprivation, indicating extramitochondrial roles for TRIAP1 in lipid homeostasis and metabolic stress adaptation. |
shRNA stable knockdown, electron microscopy (mitochondrial ultrastructure), cardiolipin quantification, metabolomics, p53 pathway reporter assays, glutamine deprivation survival assays |
Frontiers in oncology |
Medium |
36387192
|
| 2020 |
TRIAP1 knockdown in NSCLC cells (A549, H460) decreases expression of multiple antioxidant proteins (TMX1, TMX2, TXN, GLRX2, GLRX3, PRDX3, PRDX4, PRDX6), impairs radiation-induced upregulation of these proteins, and increases intracellular reactive oxygen species, thereby reducing radioresistance. |
siRNA knockdown, western blotting for antioxidant proteins, ROS measurement, cell viability and apoptosis assays after irradiation |
Thoracic cancer |
Low |
32096592
|