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PMID:23646141

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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

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


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:HIG1A

GO:0005634: nucleus

ECO:0000314:

C

Figure 1E.

complete
CACAO 8249

MOUSE:HIG1A

GO:0005739: mitochondrion

ECO:0000314:

C

Figure 1D.

complete
CACAO 8250

MOUSE:HIG1A

GO:0005515: protein binding

ECO:0000314:

F

Figure 2Cii demonstrated protein interaction between the HIGD1A and AIF (uniprot ID: Q970X1).

complete
CACAO 8251

MOUSE:HIG1A

part_of

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:HIG1A

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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