Fusion of the Endoplasmic Reticulum and Mitochondrial Outer Membrane in Rats Brown Adipose Tissue: Activation of Thermogenesis by Ca2+

Abstract

Brown adipose tissue (BAT) mitochondria thermogenesis is regulated by uncoupling protein 1 (UCP 1), GDP and fatty acids. In this report, we observed fusion of the endoplasmic reticulum (ER) membrane with the mitochondrial outer membrane of rats BAT. Ca2+-ATPase (SERCA 1) was identified by immunoelectron microscopy in both ER and mitochondria. This finding led us to test the Ca2+ effect in BAT mitochondria thermogenesis. We found that Ca2+ increased the rate of respiration and heat production measured with a microcalorimeter both in coupled and uncoupled mitochondria, but had no effect on the rate of ATP synthesis. The Ca2+ concentration needed for half-maximal activation varied between 0.08 and 0.11 µM. The activation of respiration was less pronounced than that of heat production. Heat production and ATP synthesis were inhibited by rotenone and KCN.Liver mitochondria have no UCP1 and during respiration synthesize a large amount of ATP, produce little heat, GDP had no effect on mitochondria coupling, Ca2+ strongly inhibited ATP synthesis and had little or no effect on the small amount of heat released. These finding indicate that Ca2+ activation of thermogenesis may be a specific feature of BAT mitochondria not found in other mitochondria such as liver.

Cell Death and Survival Through the Endoplasmic Reticulum- Mitochondrial Axis

“…This is consistent with studies demonstrating that ER and mitochondria trafficking along acetylated microtubules promotes ER-mitochondrial contacts predominantly in the perinuclear region [29]. Accordingly, the physiological importance of ER-mitochondria coupling has also been addressed in brown adipose tissue in which specific ER regions form a bud-like structure that is in close apposition to mitochondria [98]. These specific structures have not been observed in other tissues and may be involved in thermogenic mechanisms unique to brown adipose tissue, however, the exact role and regulation of these contact sites has not yet been elucidated.…”

Mitochondrial and sarcoplasmic reticulum abnormalities in cancer cachexia: Altered energetic efficiency?

“…The increased Ca 2+ levels induce a decrease in ATP content not only by OXPHOS dysfunction, but also through thermogenic processes, such as those performed through ANT1. Recent evidences describes SERCA not only as a heat pump, functioning like a thermogenic device in the skeletal muscle, but also as a directly regulator of Ca 2+ signaling in mitochondria [49,50]. These facts lead to suggest that the main energy dissipation observed in cachexia could be related to an increased expression of SERCA, more precisely by implication of SERCA reactions that produce heat and also lead to Ca 2+ leak.…”

New Insights into the Role of Mitochondria-Associated Endoplasmic Reticulum Membrane

“…A majority of cells examined have the type 1 structure, where most of each mitochondrion forms a single and limited contact with an ER tubule. In brown adipose tissue, some mitochondria are covered about 50% with an ER protrusion (de Meis et al, 2010). Type 2 MAM is found in 80% of unstimulated porcine tracheal smooth muscle cells (Dai et al, 2005).…”