Human VDAC Pseudogenes: an Emerging Role for VDAC1P8 Pseudogene in Acute Myeloid Leukemia

Overview

Journal Biol Res

Specialty Biology

Date 2023 Jun 21

PMID 37344914

Authors

Xena Giada Pappalardo

Pierpaolo Risiglione

Federica Zinghirino

Angela Ostuni

Daniela Luciano

Faustino Bisaccia

Vito De Pinto

Francesca Guarino

Angela Messina

Affiliations

Soon will be listed here.

Abstract

Background: Voltage-dependent anion selective channels (VDACs) are the most abundant mitochondrial outer membrane proteins, encoded in mammals by three genes, VDAC1, 2 and 3, mostly ubiquitously expressed. As 'mitochondrial gatekeepers', VDACs control organelle and cell metabolism and are involved in many diseases. Despite the presence of numerous VDAC pseudogenes 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 VDAC genes, both in physiological and in pathological contexts. Using high-throughput tools and querying many genomic and transcriptomic databases, we show that some VDAC pseudogenes are transcribed in specific tissues and pathological contexts. The obtained experimental data confirm an association of the VDAC1P8 pseudogene with acute myeloid leukemia (AML).

Conclusions: Our in-silico comparative analysis between the VDAC1 gene and its VDAC1P8 pseudogene, together with experimental data produced in AML cellular models, indicate a specific over-expression of the VDAC1P8 pseudogene in AML, correlated with a downregulation of the parental VDAC1 gene.

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