Cu/Zn Superoxide Dismutase (SOD1), the most important antioxidant defense against ROS in eukaryotic cells, localizes in cytosol and intermembrane space of mitochondria (IMS). Several evidences show a SOD1 intersection with both fermentative and respiratory metabolism. The Voltage Dependent Anion Channel (VDAC) is the main pore-forming protein in the mitochondrial outer membrane (MOM), and is considered the gatekeeper of mitochondrial metabolism. Saccharomyces cerevisiae lacking VDAC1 (Delta por1) is a very convenient model system, since it shows an impaired growth rate on non-fermentable carbon source. Transformation of Delta por1 yeast with human SOD1 completely restores the cell growth deficit in non-fermentative conditions and re-establishes the physiological levels of ROS, as well as the mitochondrial membrane potential. No similar result was found upon yeast SOD1 overexpression. A previous report highlighted the action of SOD1 as a transcription factor. Quantitative Real-Time PCR showed that beta-barrel outer-membrane encoding-genes port, tom40, sam50 are induced by hSOD1, but the same effect was not obtained in Delta por1 Delta por2 yeast, indicating a crucial function for yVDAC2. Since the lack of VDAC1 in yeast can be considered a stress factor for the cell, hSOD1 could relieve it stimulating the expression of genes bringing to the recovery of the MOM function. Our results suggest a direct influence of SOD1 on VDAC. (C) 2016 Elsevier B.V. All rights reserved.
|Titolo:||Overexpression of human SOD1 in VDAC1-less yeast restores mitochondrial functionality modulating beta-barrel outer membrane protein genes.|
|Data di pubblicazione:||2016|
|Citazione:||Overexpression of human SOD1 in VDAC1-less yeast restores mitochondrial functionality modulating beta-barrel outer membrane protein genes. / Magrì A; Di Rosa MC; Tomasello MF; Guarino F; Reina S; Messina A; De Pinto V.. - In: BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS. - ISSN 0005-2728. - 1857:6(2016), pp. 789-798.|
|Appare nelle tipologie:||1.1 Articolo in rivista|