Abstract
Mitochondria are intracellular organelles involved in a myriad of activities. To safeguard their vital functions, mitochondrial quality control (MQC) systems are in place to support organelle plasticity as well as physical and functional connections with other cellular compartments. In particular, mitochondrial interactions with the endosomal compartment support the shuttle of ions and metabolites across organelles, while those with lysosomes ensure the recycling of obsolete materials. The extrusion of mitochondrial components via the generation and release of mitochondrial-derived vesicles (MDVs) has recently been described. MDV trafficking is now included among MQC pathways, possibly operating via mitochondrial–lysosomal contacts. Since mitochondrial dysfunction is acknowledged as a hallmark of aging and a major pathogenic factor of multiple age-associated conditions, the analysis of MDVs and, more generally, of extracellular vesicles (EVs) is recognized as a valuable research tool. The dissection of EV trafficking may help unravel new pathophysiological pathways of aging and diseases as well as novel biomarkers to be used in research and clinical settings. Here, we discuss (1) MQC pathways with a focus on mitophagy and MDV generation; (2) changes of MQC pathways during aging and their contribution to inflamm-aging and progeroid conditions; and (3) the relevance of MQC failure to several disorders, including neurodegenerative conditions (i.e., Parkinson’s disease, Alzheimer’s disease) and cardiovascular disease.
Highlights
Mitochondria are intracellular organelles that participate in most biological processes by ensuring energy supply, iron, and calcium buffering, signaling through reactive oxygen species, steroid hormone and heme biosynthesis, and control of cell death/survival pathways [1,2]
We discuss (1) canonical mitochondrial quality control (MQC) pathways with a special focus on mitophagy and mitochondrial-derived vesicles (MDVs) generation; (2) changes of MQC pathways during aging and their contribution to inflamm-aging and progeroid conditions; and (3) the relevance of MQC failure to several disorders, including neurodegenerative conditions such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and cardiovascular disease (CVD)
The phosphatase and tensin homolog-induced kinase 1 (PINK1)/Parkin-independent pathway of mitophagy relies on the activity of a set of outer mitochondrial membrane (OMM)-localized receptors, including B-cell lymphoma 2 (BCL2)-interacting protein 3 like (BNIP3L/NIX), FUN14 domain-containing 1 (FUNDC1), BNIP3, autophagy, and Beclin-1 regulator 1 (AMBRA1), BCL2-like 13 (BCL2L13), FKBP prolyl isomerase 8 (FKBP8), and disrupted-in-schizophrenia-1 (DISC1) [33] (Figure 1)
Summary
Mitochondria are intracellular organelles that participate in most biological processes by ensuring energy supply, iron, and calcium buffering, signaling through reactive oxygen species, steroid hormone and heme biosynthesis, and control of cell death/survival pathways [1,2]. The establishment of mitochondrial-lysosomal contact sites has recently been included among the mechanisms participating in MQC as an additional layer of quality check involving crosstalk between the two organelles and culminating in the release of extracellular vesicles (EVs) [24]. Down this alternative degradative route, mildly damaged mitochondrial components are processed and disposed of within EVs of mitochondrial origin (mitochondrial-derived vesicles, MDVs) [25]. We discuss (1) canonical MQC pathways with a special focus on mitophagy and MDV generation; (2) changes of MQC pathways during aging and their contribution to inflamm-aging and progeroid conditions; and (3) the relevance of MQC failure to several disorders, including neurodegenerative conditions such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and cardiovascular disease (CVD)
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