| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1941934 | Biochimica et Biophysica Acta (BBA) - Bioenergetics | 2016 | 10 Pages |
•VDAC1-deficient yeast has a reduced mitochondrial activity.•hSOD1 overexpression restores mitochondrial functionality of VDAC1-less yeast.•Gene expression of β-barrel MOM proteins increases in the presence of hSOD1.•yVDAC2 is the main actor of mitochondrial reactivation promoted by hSOD1.
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 (Δpor1) is a very convenient model system, since it shows an impaired growth rate on non-fermentable carbon source. Transformation of Δpor1 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 β-barrel outer-membrane encoding-genes por2, tom40, sam50 are induced by hSOD1, but the same effect was not obtained in Δpor1Δpor2 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.
Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (139 K)Download as PowerPoint slide
