Abstract:Endoplasmic reticulum-mitochondria contact sites (ERMCSs) are dynamic contact regions with a distance of 10-30 nm between the endoplasmic reticulum and mitochondria. Endoplasmic reticulum-mitochondria contact sites regulate various biological processes, including lipid transfer, calcium homeostasis, autophagy, and mitochondrial dynamics. The dysfunction of ERMCS is closely associated with various neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. … Show more
“…MFN2 is also enriched at mitochondria–ER contact sites, likely as a tether between the mitochondria and the ER. Several ER integral membrane proteins, such as the B-cell receptor-associated protein 31 (Bap31) and vesicle-associated membrane protein (VAMP)-associated protein B (VAPB), are also critical for mitochondria–ER contact [ 7 , 13 ]. Bap31 is an ER chaperone protein that binds with the mitochondrial outer membrane protein Fis1 in the MAM, which regulates apoptosis [ 14 ].…”
Emerging evidence suggests that mitochondrion–endoplasmic reticulum (ER) and mitochondrion–lipid droplet (LD) contact sites are critical in regulating lipid metabolism in cells. It is well established that intracellular organelles communicate with each other continuously through membrane contact sites to maintain organelle function and cellular homeostasis. The accumulation of LDs in hepatocytes is an early indicator of non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), which may indicate a breakdown in proper inter-organelle communication. In this review, we discuss previous findings in mitochondrion–ER and mitochondrion–LD contact, focusing on their roles in lipid metabolism in hepatocytes. We also present evidence of a unique mitochondrion–LD contact structure in hepatocytes under various physiological and pathological conditions and propose a working hypothesis to speculate about the role of these structures in regulating the functions of mitochondria and LDs and their implications in NAFLD and ALD.
“…MFN2 is also enriched at mitochondria–ER contact sites, likely as a tether between the mitochondria and the ER. Several ER integral membrane proteins, such as the B-cell receptor-associated protein 31 (Bap31) and vesicle-associated membrane protein (VAMP)-associated protein B (VAPB), are also critical for mitochondria–ER contact [ 7 , 13 ]. Bap31 is an ER chaperone protein that binds with the mitochondrial outer membrane protein Fis1 in the MAM, which regulates apoptosis [ 14 ].…”
Emerging evidence suggests that mitochondrion–endoplasmic reticulum (ER) and mitochondrion–lipid droplet (LD) contact sites are critical in regulating lipid metabolism in cells. It is well established that intracellular organelles communicate with each other continuously through membrane contact sites to maintain organelle function and cellular homeostasis. The accumulation of LDs in hepatocytes is an early indicator of non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), which may indicate a breakdown in proper inter-organelle communication. In this review, we discuss previous findings in mitochondrion–ER and mitochondrion–LD contact, focusing on their roles in lipid metabolism in hepatocytes. We also present evidence of a unique mitochondrion–LD contact structure in hepatocytes under various physiological and pathological conditions and propose a working hypothesis to speculate about the role of these structures in regulating the functions of mitochondria and LDs and their implications in NAFLD and ALD.
“…Only 20% of spines contain ER and both ER and mitochondria cluster around actively potentiated spines 14 . Dysregulation of mitochondria and ER coupling have been demonstrated in neurodegenerative diseases such as Alzheimer’s 15 – 17 and Parkinson’s 17 , 18 , although the underlying mechanisms are yet to be elucidated. Fig.…”
Spatiotemporal compartmentation of calcium dynamics is critical for neuronal function, particularly in postsynaptic spines. This exquisite level of Ca2+ compartmentalization is achieved through the storage and release of Ca2+ from various intracellular organelles particularly the endoplasmic reticulum (ER) and the mitochondria. Mitochondria and ER are established storage organelles controlling Ca2+ dynamics in neurons. Mitochondria also generate a majority of energy used within postsynaptic spines to support the downstream events associated with neuronal stimulus. Recently, high resolution microscopy has unveiled direct contact sites between the ER and the mitochondria (MERCs), which directly channel Ca2+ release from the ER into the mitochondrial membrane. In this study, we develop a computational 3D reaction-diffusion model to investigate the role of MERCs in regulating Ca2+ and ATP dynamics. This spatiotemporal model accounts for Ca2+ oscillations initiated by glutamate stimulus of metabotropic and ionotropic glutamate receptors and Ca2+ changes in four different compartments: cytosol, ER, mitochondria, and the MERC microdomain. Our simulations predict that the organization of these organelles and inter-organellar contact sites play a key role in modulating Ca2+ and ATP dynamics.We further show that the crosstalk between geometry (mitochondria and MERC) and metabolic parameters (cytosolic ATP hydrolysis, ATP generation) influences the neuronal energy state. Our findings shed light on the importance of organelle interactions in predicting Ca2+ dynamics in synaptic signaling. Overall, our model predicts that a combination of MERC linkage and mitochondria size is necessary for optimal ATP production in the cytosol.
“…The ER and mitochondria form contacts at mitochondrial-associated membranes (MAMs) and are essential for a number of cellular functions such as calcium homeostasis, regulation of apoptosis, lipid synthesis and trafficking and energy production (reviewed in [ 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 ]). Defective ER-mitochondria linkage has recently been implicated in several neurodegenerative conditions underlying its importance for axon maintenance [ 275 , 276 , 277 , 278 , 279 ].…”
Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies for boosting axon regeneration after injury, with the goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that various axonal organelles are important centers for organizing the molecular mechanisms and machinery required for growth cone development and axon extension, and these have recently been targeted to stimulate robust regeneration in the injured adult central nervous system (CNS). This review summarizes recent literature highlighting a central role for organelles such as recycling endosomes, the endoplasmic reticulum, mitochondria, lysosomes, autophagosomes and the proteasome in developmental axon growth, and describes how these organelles can be targeted to promote axon regeneration after injury to the adult CNS. This review also examines the connections between these organelles in developing and regenerating axons, and finally discusses the molecular mechanisms within the axon that are required for successful axon growth.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
