Super‐Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore

Chen, Qixin; Jin, Chengzhi; Shao, Xintian; Guan, Ruilin; Tian, Ze; Wang, Chenran; Liu, Fei; Ling, Peixue; Guan, Jun‐Lin; Ji, Liang; Wang, Fengshan; Chao, Hui; Diao, Jiajie

doi:10.1002/smll.201802166

Cited by 100 publications

(66 citation statements)

References 47 publications

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“…These structures do not involve metabolite transfer between tethering organelles nor are they required for autophagosome biogenesis or mitophagy as shown by the fact that they are void of autophagosomal markers (e.g., unc-51 like autophagy activating kinase (ULK1), Atg5, Atg12, and LC3) [14]. The independence of mitochondrial-lysosomal contact sites from mitophagy has been further confirmed in cells knocked out for autophagy receptors (i.e., NDP52, OPTN, neighbor of BRCA1 gene 1 protein (NBR1), tax1-binding protein 1 (TAX1BP1), and p62) in which the genetic ablation does not interfere with mitochondrial-lysosomal contact formation [83].…”

Section: Nondegradative Pathwaysmentioning

confidence: 94%

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

Picca

Calvani

Coelho-Júnior

et al. 2020

Cells

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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 Ca 2+ 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.Cells 2020, 9, 598 2 of 18 instability, telomere attrition, epigenetic alterations, deregulated nutrient sensing, and stem cell exhaustion [3]. According to the geroscience hypothesis, perturbations in these mechanisms increase the susceptibility to most chronic diseases, functional loss, and eventually, death [4]. Hence, these biologic pillars represent ideal targets for interventions to foster healthy aging [5,6].Mitochondrial dysfunction has attracted considerable interest as a target for geroprotective interventions. Indeed, mitochondria play sensor-transducer-effector roles in a multitude of biological processes, including integration of cell death signaling and preservation of cell stemness [7,8]. Albeit long considered to be standalone organelles, a great deal of evidence indicates that mitochondria interact physically and functionally with other cellular compartments via membrane contact sites and tethering molecules [9,10]. In particular, mitochondria establish connections with the endosomal compartment [11,12] and lysosomes [13,14]. These interactions support cytosolic shuttle systems of ions and metabolites across organelles [10,15], and participate to the regulation of cellular housekeeping processes [13,14].The mitochondrial-lysosomal axis is a major actor in mitochondrial quality control (MQC), a hierarchical network of pathways that ensure organellar homeostasis through the coordination of mitochondrial proteostasis, dynamics, biogene...

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Section: Nondegradative Pathwaysmentioning

confidence: 94%

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

Picca

Calvani

Coelho-Júnior

et al. 2020

Cells

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“…However, in HeLa cells, mutation in Rab7, Fis1 or TBC1D15 prevents the recruitment of TBC1D15 to the mitochondria, resulting in an increase in the duration of mitochondria-lysosome contact site, causing accumulation of enlarged lysosomes and impairment in mitochondrial fission events ( Figure 3B, step 1) [139]. However, the lysosome-mitochondria MCS formation was not prevented by the penta knockout (p62, NDP52, OPTN, NBR1 and TAX1BP1) of mitophagy markers in Hela cells, suggesting that MCS formation is independent of the process of mitophagy [138].…”

Section: Lysosome-mitochondria Contact Sitementioning

confidence: 99%

Section: Lysosome-mitochondria Contact Sitementioning

confidence: 99%

“…Mitochondrial and lysosomal membranes are apart from each other by a distance of~10 nm, making it ideal for MCS formation between the two organelles [138,139]. Approximately 15% of lysosomes form a contact site with mitochondria [138]. Recently, Wong et al, demonstrated that lysosomes and mitochondria form a stable MCS, which is induced by the lysosomal GTP-bound Rab7 protein, highlighting the bidirectional regulation of lysosome and mitochondrial dynamics [139].…”

Section: Lysosome-mitochondria Contact Sitementioning

confidence: 99%

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Lysosomal Biology and Function: Modern View of Cellular Debris Bin

Trivedi

Bartlett

Pulinilkunnil

2020

Cells

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150

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Lysosomes are the main proteolytic compartments of mammalian cells comprising of a battery of hydrolases. Lysosomes dispose and recycle extracellular or intracellular macromolecules by fusing with endosomes or autophagosomes through specific waste clearance processes such as chaperone-mediated autophagy or microautophagy. The proteolytic end product is transported out of lysosomes via transporters or vesicular membrane trafficking. Recent studies have demonstrated lysosomes as a signaling node which sense, adapt and respond to changes in substrate metabolism to maintain cellular function. Lysosomal dysfunction not only influence pathways mediating membrane trafficking that culminate in the lysosome but also govern metabolic and signaling processes regulating protein sorting and targeting. In this review, we describe the current knowledge of lysosome in influencing sorting and nutrient signaling. We further present a mechanistic overview of intra-lysosomal processes, along with extra-lysosomal processes, governing lysosomal fusion and fission, exocytosis, positioning and membrane contact site formation. This review compiles existing knowledge in the field of lysosomal biology by describing various lysosomal events necessary to maintain cellular homeostasis facilitating development of therapies maintaining lysosomal function.

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“…Cell imaging combined with platinum sensor or luminescent tag is ap owerful method for non-invasively tracking platinum drugs in live cells.Among different microscopies for cell imaging, super-resolution microscopy provides as uperresolution imaging technique to break the optical diffraction limit, and realizes the super-resolution monitoring of the dynamic changes of organelles and drugs screening. [9] Among them, super-resolution microscopy based on SIM (Structured Illumination Microscopy) is favored by researchers because of its advantages such as wavelength diversity,f ast imaging and simple sample preparation. [10] It has been widely used for organelle interaction, organoids imaging, drug screening and so on.…”

Section: Introductionmentioning

confidence: 99%

Multiple‐Color Platinum Complex with Super‐Large Stokes Shift for Super‐Resolution Imaging of Autolysosome Escape

et al. 2020

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It is of great significance to track the platinum drugs in real time with super-resolution to elucidate their mechanism of action, such as their behavior and distribution in live cells. Such information is required for further drug development. However,itisalways challenging to design platinum complexes suitable for such research. Herein, we design al uminescent building block(L)f or metal complexes and ad inuclear platinum complex (Pt 2 L)f or super-resolution imaging.B ecause of its super-large Stokes shift and excellent photophysical properties, Pt 2 L is capable of serving as an ideal candidate for super-resolution imaging with extremely low luminescence background and high photobleaching resistance.M oreover, upon light stimulation, am atter flux of Pt 2 L escaping from autolysosomes to nucleus was observed, whichr epresents anew transportation path. Utilizing the photoactivated escape properties,w ec an regulate the nuclear accessibility of Pt 2 L form autolysosomes with photo-selectivity,w hichp rovides anew way to improve the targeting of platinum drugs.

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Super‐Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore

Cited by 100 publications

References 47 publications

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

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

Lysosomal Biology and Function: Modern View of Cellular Debris Bin

Multiple‐Color Platinum Complex with Super‐Large Stokes Shift for Super‐Resolution Imaging of Autolysosome Escape

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