Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX MFN2 OE]

ABSTRACT: Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX MFN2 OE]

PROVIDER: PRJNA918403 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX MFN2 OE]

Project description:Mitochondrial metabolism recently emerged as a critical dependency in acute myeloid leukemia (AML). The shape of mitochondria is tightly regulated by dynamin GTPase proteins, which drive opposing fusion and fission forces to consistently adapt bioenergetics to the cellular context. Here, we showed that targeting mitochondrial structure through the inhibition of mitochondrial fusion was a new vulnerability of AML cells, when assayed in patient-derived xenograft (PDX) models. Genetic depletion of mitofusin 2 (MFN2) or optic atrophy 1 (OPA1) or pharmacological inhibition of OPA1 (MYLS22) blocked mitochondrial fusion and had significant anti-leukemic activity, while having limited impact on normal hematopoietic cells ex vivo and in vivo. Mechanistically, inhibition of mitochondrial fusion disrupted mitochondrial respiration and reactive oxygen species production, leading to cell cycle arrest at the G0/G1 transition. These results nominate the inhibition of mitochondrial fusion as a promising therapeutic approach for AML.

2023-03-16 | GSE222166 | GEO

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shOPA1]

2023-03-16 | GSE222168 | GEO

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shMFN2]

2023-03-16 | GSE222167 | GEO

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shOPA1]

Project description:Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shOPA1]

| PRJNA918401 | ENA

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shMFN2]

Project description:Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shMFN2]

| PRJNA918402 | ENA

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [Cell lines shCTL shMFN2]

2023-03-16 | GSE222165 | GEO

STAT6 in mitochondrial outer membrane impairs mitochondrial fusion by inhibiting MFN2 dimerization

Project description:Although it is reported that mitochondria-localized nuclear transcription factors (TFs) regulate mitochondrial processes such as apoptosis and mitochondrial transcription/respiration, their functions and mechanisms of mitochondrial dynamics regulated by mitochondria-localized nuclear TFs are yet to be fully characterized. Here, we identify STAT6 as a mitochondrial protein that is localized in the outer membrane of mitochondria (OMM). In addition to regulating mitochondrial gene expression as a nuclear TF, STAT6 in OMM inhibits mitochondrial fusion by blocking MFN2 dimerization. This implies that STAT6 has dual role in overall mitochondrial process. Moreover, mitochondrial accumulation of STAT6 in response to these findings reveal that STAT6 is a new regulator of mitochondrial processes including mitochondrial biogenesis and fusion/fission mechanisms.

2024-04-01 | GSE255693 | GEO

STAT6 in mitochondrial outer membrane impairs mitochondrial fusion by inhibiting MFN2 dimerization

Project description:STAT6 in mitochondrial outer membrane impairs mitochondrial fusion by inhibiting MFN2 dimerization

| PRJNA1076171 | ENA

USP28-regulated mitochondrial homeostasis mechanism that involves the PPARα-Mfn2 axis in diabetic hearts [ChIP-seq]

Project description:The majority of diabetics are susceptible to cardiac dysfunction and heart failure, while conventional drug therapy cannot correct diabetic cardiomyopathy (DCM) progression. Herein, we assessed the potential role and therapeutic value of ubiquitin-specific protease 28 (USP28) on the metabolic vulnerability of DCM. PPARα-/- in the db/db background mice were constructed to check the mechanism of USP28 in vivo. Inducible cardiac-specific deletion of Mfn2 in the db/db background mice was utilized to evaluate USP28-mediated cardioprotection. chromatin immunoprecipitation (ChIP) assays revealed that PPARα promote mitofusin 2 (Mfn2) transcription, thereby impeding mitochondrial morphofunctional defects.

2023-10-15 | GSE244905 | GEO

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia.

Project description:Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia.

| PRJNA918400 | ENA