Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Mar;94(3):335-46.
doi: 10.1007/s00109-015-1359-y. Epub 2015 Nov 4.

Restoration of Opa1-long isoform inhibits retinal injury-induced neurodegeneration

Yue Sun  1 , Weili Xue  1 , Zhiyin Song  1 , Kun Huang  2 , Ling Zheng  3
Affiliations

Restoration of Opa1-long isoform inhibits retinal injury-induced neurodegeneration

Yue Sun et al. J Mol Med (Berl). 2016 Mar.

Abstract

Optic atrophy 1 (Opa1) is a critical factor that regulates fusion and other important functions of mitochondria. In mitochondrion, the N-terminal mitochondrial targeting sequence of Opa1 precursors is removed to generate Opa1 long isoforms (L-Opa1), which are further cleaved into short isoforms (S-Opa1). In the present study, we found that retinal ischemia-reperfusion (I/R) injury and intravitreal injection of carbonylcyanide m-chlorophenyl hydrazone (CCCP) both dramatically induced Opa1 cleavage and caused loss of L-Opa1. In cultured neuronal cells under hypoxia-reoxygenation (H/R) injury, similar changes for Opa1 were also observed. In contrast, restoration of L-Opa1 level by overexpression of S1 cleavage site deletion Opa1 splice 1 (Opa1-ΔS1) not only normalized the H/R-induced mitochondrial morphology changes, but also inhibited the H/R-induced apoptosis, necrosis, and the intracellular ATP loss. Furthermore, recovering L-Opa1 level in the I/R-injured retina by intravitreal injection of genipin or overexpression of Opa1-ΔS1 inhibited apoptosis, necrosis, cell loss in the ganglion cell layer and retinal thickness reduction. Together, our data demonstrated the loss of L-Opa1 is involved in the development of retinal I/R injury, indicating restoring L-Opa1 level may be considered as a therapeutic target for I/R injury-related diseases, at least for the retina. Key messages: Retinal ischemia-reperfusion (I/R) or hypoxia-reoxygenation (H/R) injury induces L-Opa1 loss. Opa1-ΔS1 overexpression inhibits H/R-induced L-Opa1 loss. Opa1-ΔS1 overexpression inhibits H/R-induced mitochondria morphology change. Opa1-ΔS1 and genipin inhibit retinal I/R injury-induced necroptosis. Opa1-ΔS1 and genipin inhibit retinal I/R injury-induced neurodegeneration.

Keywords: Apoptosis and necrosis; Genipin; Neurodegeneration; Opa1; Retinal injury.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cell. 2009 Jun 12;137(6):1112-23 - PubMed
    1. Nat Cell Biol. 2009 Aug;11(8):958-66 - PubMed
    1. Adv Exp Med Biol. 2014;801:145-54 - PubMed
    1. Int J Mol Sci. 2014 Mar 26;15(4):5304-22 - PubMed
    1. Acta Pharmacol Sin. 2011 Sep;32(9):1089-99 - PubMed

Publication types

MeSH terms

LinkOut - more resources