Abstract
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 (HlAIF-2) from the tropical sea cucumber Holothuria leucospilota. HlAIF-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 HlAIF-2. HlAIF-2 mRNA was ubiquitously detected in all tissues and increased significantly during larval development. The transcript expression of HlAIF-2 was significantly upregulated after treatment with CdCl2, but not the pathogen-associated molecular patterns (PAMPs) in primary coelomocytes. In HEK293T cells, HlAIF-2 protein was located in the cytoplasm and nucleus, and tended to transfer into the nucleus by CdCl2 incubation. Moreover, there was an overexpression of HlAIF-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.
Highlights
Apoptosis, known as programmed cell death, is an essential biological process that plays critical roles in embryonic development, organic differentiation, and normal tissue homeostasis in metazoans [1]
The results demonstrated that H. leucospilota AIF-2 (HlAIF-2) overexpression could significantly induce apoptosis with DNA fragmentation in cell nuapoptosis rate was detected by TUNEL assay
The results demonstrated that HlAIF-2 overexpression could significantly induce apoptosis with DNA fragmentation in cell nuclei Int
Summary
Known as programmed cell death, is an essential biological process that plays critical roles in embryonic development, organic differentiation, and normal tissue homeostasis in metazoans [1]. Several caspaseindependent apoptotic pathways play important roles in the immune system, including the release of apoptosis-inducing factor (AIF) from mitochondria, which can induce caspaseindependent peripheral chromatin condensation and large-scale DNA fragmentation in the nucleus [4]. AIFs are caspase-independent death effectors that may trigger chromatin condensation and DNA fragmentation to induce apoptosis [6]. The mitochondrial localization sequence (MLS) that directs the protein to mitochondria is found in the amino-terminus of AIF-1 and AIF-3 but not AIF-2. AIF-2 retains the C-terminal domain that contains a nuclear localization sequence (NLS) that directs the protein to the nucleus and a pro-apoptotic segment that can trigger apoptosis when it is activated [6]. Mitochondria play a key role in oxidative stress-induced apoptosis; among which, AIFs mainly exercise their functions by transferring from the mitochondrial membrane to the nucleus [13]
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