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PMID:23646141
Citation |
Ameri, K, Rajah, AM, Nguyen, V, Sanders, TA, Jahangiri, A, Delay, M, Donne, M, Choi, HJ, Tormos, KV, Yeghiazarians, Y, Jeffrey, SS, Rinaudo, PF, Rowitch, DH, Aghi, M and Maltepe, E (2013) Nuclear Localization of the Mitochondrial Factor HIGD1A during Metabolic Stress. PLoS ONE 8:e62758 |
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Abstract |
Cellular stress responses are frequently governed by the subcellular localization of critical effector proteins. Apoptosis-inducing Factor (AIF) or Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH), for example, can translocate from mitochondria to the nucleus, where they modulate apoptotic death pathways. Hypoxia-inducible gene domain 1A (HIGD1A) is a mitochondrial protein regulated by Hypoxia-inducible Factor-1α (HIF1α). Here we show that while HIGD1A resides in mitochondria during physiological hypoxia, severe metabolic stress, such as glucose starvation coupled with hypoxia, in addition to DNA damage induced by etoposide, triggers its nuclear accumulation. We show that nuclear localization of HIGD1A overlaps with that of AIF, and is dependent on the presence of BAX and BAK. Furthermore, we show that AIF and HIGD1A physically interact. Additionally, we demonstrate that nuclear HIGD1A is a potential marker of metabolic stress in vivo, frequently observed in diverse pathological states such as myocardial infarction, hypoxic-ischemic encephalopathy (HIE), and different types of cancer. In summary, we demonstrate a novel nuclear localization of HIGD1A that is commonly observed in human disease processes in vivo. |
Links |
PubMed PMC3639984 Online version:10.1371/journal.pone.0062758 |
Keywords |
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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
GO:0005634: nucleus |
ECO:0000314: |
C |
Figure 1E. |
complete | ||||
GO:0005739: mitochondrion |
ECO:0000314: |
C |
Figure 1D. |
complete | ||||
GO:0005515: protein binding |
ECO:0000314: |
F |
Figure 2Cii demonstrated protein interaction between the HIGD1A and AIF (uniprot ID: Q970X1). |
complete | ||||
part_of |
GO:0005739: mitochondrion |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
part_of |
GO:0005634: nucleus |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
See also
References
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