Apoptosis-Inducing Factor 2 (AIF-2) Mediates a Caspase-Independent Apoptotic Pathway in the Tropical Sea Cucumber (<i>Holothuria leucospilota</i>)
Apoptosis, also known as programmed cell death, is a biological process that is critical for embryonic development, organic differentiation, and tissue homeostasis of organisms. As an essential mitochondrial flavoprotein, the apoptosis-inducing factor (AIF) can directly mediate the caspase-independe...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/6/3008 |
| Summary: | Apoptosis, also known as programmed cell death, is a biological process that is critical for embryonic development, organic differentiation, and tissue homeostasis of organisms. As an essential mitochondrial flavoprotein, the apoptosis-inducing factor (AIF) can directly mediate the caspase-independent mitochondrial apoptotic pathway. In this study, we identified and characterized a novel AIF-2 (<i>Hl</i>AIF-2) from the tropical sea cucumber <i>Holothuria leucospilota</i>. <i>Hl</i>AIF-2 contains a conserved Pyr_redox_2 domain and a putative C-terminal nuclear localization sequence (NLS) but lacks an N-terminal mitochondrial localization sequence (MLS). In addition, both NADH- and FAD-binding domains for oxidoreductase function are conserved in <i>Hl</i>AIF-2. <i>Hl</i>AIF-2 mRNA was ubiquitously detected in all tissues and increased significantly during larval development. The transcript expression of <i>Hl</i>AIF-2 was significantly upregulated after treatment with CdCl<sub>2</sub>, but not the pathogen-associated molecular patterns (PAMPs) in primary coelomocytes. In HEK293T cells, <i>Hl</i>AIF-2 protein was located in the cytoplasm and nucleus, and tended to transfer into the nucleus by CdCl<sub>2</sub> incubation. Moreover, there was an overexpression of <i>Hl</i>AIF-2-induced apoptosis in HEK293T cells. As a whole, this study provides the first evidence for heavy metal-induced apoptosis mediated by AIF-2 in sea cucumbers, and it may contribute to increasing the basic knowledge of the caspase-independent apoptotic pathway in ancient echinoderm species. |
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| ISSN: | 1661-6596 1422-0067 |