TY - JOUR
T1 - Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View
AU - Calvani, Riccardo
AU - Landi, Francesco
AU - Bernabei, Roberto
AU - Marzetti, Emanuele
PY - 2020
Y1 - 2020
N2 - Mitochondrial dysfunction and failing mitochondrial quality control (MQC) are major determinants of aging. Far from being standalone organelles, mitochondria are intricately related with cellular other compartments, including lysosomes. The intimate relationship between mitochondria and lysosomes is reflected by the fact that lysosomal degradation of dysfunctional mitochondria is the final step of mitophagy. Inter-organelle membrane contact sites also allow bidirectional communication between mitochondria and lysosomes as part of nondegradative pathways. This interaction establishes a functional unit that regulates metabolic signaling, mitochondrial dynamics, and, hence, MQC. Contacts of mitochondria with the endoplasmic reticulum (ER) have also been described. ER-mitochondrial interactions are relevant to Ca2+ homeostasis, transfer of phospholipid precursors to mitochondria, and integration of apoptotic signaling. Many proteins involved in mitochondrial contact sites with other organelles also participate to degradative MQC pathways. Hence, a comprehensive assessment of mitochondrial dysfunction during aging requires a thorough evaluation of degradative and nondegradative inter-organelle pathways. Here, we present a geroscience overview on (1) degradative MQC pathways, (2) nondegradative processes involving inter-organelle tethering, (3) age-related changes in inter-organelle degradative and nondegradative pathways, and (4) relevance of MQC failure to inflammaging and age-related conditions, with a focus on Parkinson's disease as a prototypical geroscience condition.
AB - Mitochondrial dysfunction and failing mitochondrial quality control (MQC) are major determinants of aging. Far from being standalone organelles, mitochondria are intricately related with cellular other compartments, including lysosomes. The intimate relationship between mitochondria and lysosomes is reflected by the fact that lysosomal degradation of dysfunctional mitochondria is the final step of mitophagy. Inter-organelle membrane contact sites also allow bidirectional communication between mitochondria and lysosomes as part of nondegradative pathways. This interaction establishes a functional unit that regulates metabolic signaling, mitochondrial dynamics, and, hence, MQC. Contacts of mitochondria with the endoplasmic reticulum (ER) have also been described. ER-mitochondrial interactions are relevant to Ca2+ homeostasis, transfer of phospholipid precursors to mitochondria, and integration of apoptotic signaling. Many proteins involved in mitochondrial contact sites with other organelles also participate to degradative MQC pathways. Hence, a comprehensive assessment of mitochondrial dysfunction during aging requires a thorough evaluation of degradative and nondegradative inter-organelle pathways. Here, we present a geroscience overview on (1) degradative MQC pathways, (2) nondegradative processes involving inter-organelle tethering, (3) age-related changes in inter-organelle degradative and nondegradative pathways, and (4) relevance of MQC failure to inflammaging and age-related conditions, with a focus on Parkinson's disease as a prototypical geroscience condition.
KW - biomarkers
KW - exosomes
KW - extracellular vesicles
KW - geroprotective interventions
KW - mitochondrial damage
KW - mitochondrial dynamics
KW - mitochondrial-derived vesicles
KW - mitochondrial-lysosomal axis
KW - mitophagy
KW - neurodegeneration
KW - biomarkers
KW - exosomes
KW - extracellular vesicles
KW - geroprotective interventions
KW - mitochondrial damage
KW - mitochondrial dynamics
KW - mitochondrial-derived vesicles
KW - mitochondrial-lysosomal axis
KW - mitophagy
KW - neurodegeneration
UR - http://hdl.handle.net/10807/154298
U2 - 10.3390/cells9030598
DO - 10.3390/cells9030598
M3 - Meeting Abstract
SN - 2073-4409
VL - 2020
SP - 1
EP - 19
JO - Cells
JF - Cells
ER -