Human VDACpseudogenes: an emerging role for VDAC1P8pseudogene in acute myeloid leukemia

Background: Voltage-dependent anion selective channels (VDACs) are the most abundant mitochondrial outer membrane proteins, encoded in mammals by three genes, VDAC1, 2and 3, mostly ubiquitously expressed. As 'mitochondrial gatekeepers', VDACscontrol organelle and cell metabolism and are involved in many diseases. Despite the presence of numerous VDACpseudogenes in the human genome, their significance and possible role in VDAC protein expression has not yet been considered. Results: We investigated the relevance of processed pseudogenes of human VDACgenes,both in physiological and in pathological contexts. Using high-throughput tools and querying many genomic and transcriptomic databases, we show that some VDACpseudogenes are transcribed in specific tissues and pathological contexts. The obtained experimental data confirm an association of the VDAC1P8pseudogene with acute myeloid leukemia (AML). Conclusions: Our in-silicocomparative analysis between the VDAC1gene and its VDAC1P8pseudogene, together with experimental data produced in AML cellular models, indicate a specific over-expression of the VDAC1P8pseudogene in AML, correlated with a downregulation of the parental VDAC1gene.