A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1α in a Von Hippel-Lindau Renal Oncocytoma
Joint Authors
Ceccarelli, C.
De Luise, Monica
Porcelli, Anna Maria
Guarnieri, Vito
Gasparre, Giuseppe
D'Agruma, Leonardo
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-5, 5 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-01-09
Country of Publication
Egypt
No. of Pages
5
Main Subjects
Abstract EN
The Von Hippel-Lindau (VHL) syndrome has been rarely associated with renal oncocytomas, and tumors usually show HIF1α chronic stabilization.
By contrast, oncocytomas mainly associated with respiratory chain (RC) defects due to severe mitochondrial DNA (mtDNA) mutations are incapable of stabilizing HIF1α, since oxygen consumption by the RC is dramatically diminished and prolylhydroxylase activity is increased by α-ketoglutarate accumulation following Krebs cycle slowdown.
Here, we investigate the cooccurrence of a pseudohypoxic condition with oncocytic transformation in a case of VHL-associated renal oncocytoma.
While HIF1α was abundant in nuclei concordantly with defects in VHL, negative staining of its targets carbonic anhydrase IX (CAIX) and glucose transporter GLUT1, usually overexpressed in VHL-associated neoplasms, suggested HIF1α to be present in its inactive (hydroxylated) form.
MtDNA sequencing and immunohistochemistry analyses revealed a MT-CO1 stop-gain mutation and cytochrome c oxidase loss.
We suggest that a mitochondrial respiration impairment may lead to hyperhydroxylation of the transcription factor, which we confirmed by specific staining of hydroxylated HIF1α.
Such inactive form hence accumulated in the VHL-deficient tumor, where it may contribute to the benign nature of the neoplasm.
We propose that the protumorigenic role of HIF1α in VHL cancers may be blunted through drugs inhibiting mitochondrial respiratory complexes, such as metformin.
American Psychological Association (APA)
De Luise, Monica& Guarnieri, Vito& Ceccarelli, C.& D'Agruma, Leonardo& Porcelli, Anna Maria& Gasparre, Giuseppe. 2019. A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1α in a Von Hippel-Lindau Renal Oncocytoma. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-5.
https://search.emarefa.net/detail/BIM-1205450
Modern Language Association (MLA)
De Luise, Monica…[et al.]. A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1α in a Von Hippel-Lindau Renal Oncocytoma. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-5.
https://search.emarefa.net/detail/BIM-1205450
American Medical Association (AMA)
De Luise, Monica& Guarnieri, Vito& Ceccarelli, C.& D'Agruma, Leonardo& Porcelli, Anna Maria& Gasparre, Giuseppe. A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1α in a Von Hippel-Lindau Renal Oncocytoma. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-5.
https://search.emarefa.net/detail/BIM-1205450
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205450