Cell Death and Survival Through the Endoplasmic Reticulum- Mitochondrial Axis

Abstract

The endoplasmic reticulum has a central role in biosynthesis of a variety of proteins and lipids. Mitochondria generate ATP, synthesize and process numerous metabolites, and are key regulators of cell death. The architectures of endoplasmic reticulum and mitochondria change continually via the process of membrane fusion, fission, elongation, degradation, and renewal. These structural changes correlate with important changes in organellar function. Both organelles are capable of moving along the cytoskeleton, thus changing their cellular distribution. Numerous studies have demonstrated coordination and communication between mitochondria and endoplasmic reticulum. A focal point for these interactions is a zone of close contact between them known as the mitochondrial–associated endoplasmic reticulum membrane (MAM), which serves as a signaling juncture that facilitates calcium and lipid transfer between organelles. Here we review the emerging data on how communication between endoplasmic reticulum and mitochondria can modulate organelle function and determine cellular fate.

Spontaneous activation of a MAVS-dependent antiviral signaling pathway determines high basal interferon-β expression in cardiac myocytes

“…Given that cardiac myocytes and skeletal myotubes have comparable levels of the mitochondria-associated protein MAVS (Figure 2C) but express significantly different basal levels of IFN-β (Figure 1B), MAVS abundance alone cannot be sufficient to drive spontaneous downstream signaling in cardiac myocytes. The mitochondria in cardiac myocytes are exceptionally well-associated with the sarcoplasmic reticulum (SR; the muscle-specific ER) to facilitate calcium (Ca 2+ ) transfer, reactive oxygen species (ROS) communication, and apoptotic signaling between these two organelles (10, 23, 26, 33). Our results suggest that the intrinsic association of the SR and mitochondria in cardiac myocytes likely facilitates the synthesis of basal IFN-β (Figures 3-4).…”

Redox control of vascular smooth muscle cell function and plasticity

“…1). Finally, it has been shown that the sGC-cGMP-PKG pathway regulates cytosolic Ca 2+ [101] and that mitofusion protein MFN2 is a crucial mediator of Ca 2+ flux between the mitochondria and ER [71–74]. It is therefore interesting to speculate that Ca 2+ flux may be the downstream convergence point for these pathways and the currency for SMC phenotypic switching.…”

“…The transfer of calcium (Ca 2+ ) between mitochondria and ER is important for regulating mitochondrial bioenergetics and cell viability [71–74]. The mitochondria-ER link promotes Ca 2+ flux into the mitochondria, an activity that is associated with increased ATP generation and anti-proliferative activity in SMC [75, 76].…”

The ERRor of Our Ways

“…The long-standing concept of mitochondria as free-floating cytoplasmic entities has been modified in the face of discovery that mitochondria interact via Bmembrane fusion, fission, elongation, degradation, and renewal[ with the endoplasmic reticulum (71). Indeed, mitochondria that are tethered to the ER create a mitochondria-associated endoplasmic reticulum membrane (MAM) junction, which is a focus for signaling.…”

“…Indeed, mitochondria that are tethered to the ER create a mitochondria-associated endoplasmic reticulum membrane (MAM) junction, which is a focus for signaling. Through this contact point, calcium and lipids are transferred, mediating communicating and signaling for both organelles (71,72).…”