Regulation of mitochondrial function by caveolin‐3

Abstract

Caveolae, cholesterol ‐rich invaginations of the plasma membrane, are scaffolding domains that contain caveolins, proteins involved in signaling processes in the heart. Cardiac pathologies are characterized by mitochondrial dysfunction. Mitochondria act as buffers to respond to cell stress and determine cell survival or death. Caveolins, specifically caveolin‐3 (Cav‐3), may modulate mitochondrial function during stressful events. We hypothesize that overexpression of Cav‐3 in mouse myocardium modulates mitochondrial function. Three‐month old hearts from wild‐type or Cav‐3 overexpressing (Cav‐3 OE) mice were excised, then mitochondria were isolated and purified. Pure mitochondria were subjected to a calcium challenge once per minute until the mitochondria no longer became polarized, a sign of mitochondrial dysfunction. Mitochondria from Cav‐3 OE mice were more tolerant to calcium loading suggesting that these mitochondria are more robust and may be more efficient in tolerating stress. Also, Cav‐3 OE cardiac myocytes had reduced superoxide generation in response to hypoxia/reperfusion injury. These results imply that Cav‐3 overexpression plays a role in preservation of mitochondrial function.