Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

• Published in: The international journal of biochemistry & cell biology Vol. 44; no. 1; pp. 16 - 20
• Main Authors: Bravo, Roberto, Gutierrez, Tomás, Paredes, Felipe, Gatica, Damián, Rodriguez, Andrea E., Pedrozo, Zully, Chiong, Mario, Parra, Valentina, Quest, Andrew F.G., Rothermel, Beverly A., Lavandero, Sergio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.01.2012
• Subjects: apoptosis; Biochemistry; Calcium; endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - physiology; Endoplasmic Reticulum Stress - physiology; Endoplasmic reticulum–mitochondria axis; Energy Metabolism; ER stress; homeostasis; Humans; metabolic diseases; Mitochondria - metabolism; Mitochondria - physiology; Mitochondrial bioenergetics; unfolded protein response; IP3R; Calcium; Mitochondrial bioenergetics; JNK; RyR; NFkB; UPR; SOCE; CHOP; Mfn2; ASK1; GRP78; ER stress; Endoplasmic reticulum–mitochondria axis; TRAF2; BAK; MAPK; SERCA; ER; eIF2α; IRE1α; MAM; VDAC; X-box; BAX; ATF6; ATF4; FoxO1
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2011.10.012

► The ER is the site of synthesis, folding and processing of secreted proteins, and is also the main reservoir of intracellular calcium. ► Protein misfolding activates ER signaling cascades that modulate the function of other organelles. ► The ER physically interacts with mitochondria. ► Calcium release from ER stores stimulates mitochondrial bioenergetics as an adaptive response during the early phases of ER stress. ► Prolonged, severe ER stress can lead to pathological changes in cell metabolism and eventually apoptosis. Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER–mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders.