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Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

1
Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy
2
Institute of Internal Medicine and Geriatrics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
*
Authors to whom correspondence should be addressed.
Academic Editors: Tito Calì and Marisa Brini
Cells 2020, 9(3), 598; https://doi.org/10.3390/cells9030598
Received: 17 February 2020 / Revised: 28 February 2020 / Accepted: 29 February 2020 / Published: 3 March 2020
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. View Full-Text
Keywords: biomarkers; exosomes; extracellular vesicles; geroprotective interventions; mitophagy; mitochondrial damage; mitochondrial dynamics; mitochondrial-derived vesicles; mitochondrial-lysosomal axis; neurodegeneration biomarkers; exosomes; extracellular vesicles; geroprotective interventions; mitophagy; mitochondrial damage; mitochondrial dynamics; mitochondrial-derived vesicles; mitochondrial-lysosomal axis; neurodegeneration
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Picca, A.; Calvani, R.; Coelho-Junior, H.J.; Landi, F.; Bernabei, R.; Marzetti, E. Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View. Cells 2020, 9, 598.

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