Mitochondrial Heterogeneity: Evaluating Mitochondrial Subpopulation Dynamics in Stem Cells

Woods, Dori C.

doi:10.1155/2017/7068567

Cited by 43 publications

(35 citation statements)

References 61 publications

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“…Moreover, Drp1 is widely expressed in the cytoplasm but scarely distributed on mitochondria, which only accounts for about 5%. This result is consistent with previous studies [19,20]. However, Drp1 distribution also shows the heterogeneity.…”

Section: Drp1 Expression In Human Malignant Glioma Tissue Reached Thesupporting

confidence: 93%

Drp1 widely, yet heterogeneously distributes in mice central nervous system

Luo

Dai²,

Wang

et al. 2020

Preprint

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Objectives: Drp1 is wildly expressed and plays a role in inducing mitochondrial fission process. It is confirmed that many diseases are associated with Drp1 and mitochondria. However, since the exact Drp1 is not specifically distributed, it is hard to determine the impact of anti-Drp1 molecules on human body and where the Drp1 inhibitor functions. Methods: We visualized distribution of Drp1 in different brain regions, and explicated the relationship between Drp1 and mitochondria. GAD67-GFP knock-in mice were utilized to detect the expression patterns of Drp1 on the GABAergic neurons. And we further analyzed Drp1 expression in human malignant glioma tissue. Results: Drp1 widely but heterogeneously distributed in central nervous system. Further observation indicated that Drp1 was highly and heterogeneously expressed in inhibitory neurons. Under transmission electron microscope, Drp1 distribution in dendrites was higher than other areas in neurons and only a small amount of Drp1 was located on mitochondria. In human malignant glioma, Drp1 fluorescence intensity increased from grade I-III, while grade IV showed the descending trend. Conclusion: In this study, we observed Drp1 widely yet heterogeneously distributed in central nervous system. Drp1 heterogeneous distribution may be related with the occurrence and development of neurologic disease. We hope that the relationship between Drp1 and mitochondria may give the therapeutic guidance.

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Section: Drp1 Expression In Human Malignant Glioma Tissue Reached Thesupporting

confidence: 93%

Drp1 widely, yet heterogeneously distributes in mice central nervous system

Luo

Dai²,

Wang

et al. 2020

Preprint

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“…Similarly, the APOE4 astrocytes exhibit reduced mitochondrial metabolism as measured by MTT 20 , 36 (Fig. 5c ), and by less dense cristae, which is another indicator of impaired mitochondrial activity 37 , 38 (Fig. 5d ).…”

Section: Resultsmentioning

confidence: 87%

Altered mitochondrial dynamics and function in APOE4-expressing astrocytes

et al. 2020

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APOE4 is a major risk factor for sporadic Alzheimer’s disease; however, it is unclear how it exerts its pathological effects. Others and we have previously shown that autophagy is impaired in APOE4 compared to APOE3 astrocytes, and demonstrated differences in the expression of mitochondrial dynamics proteins in brains of APOE3 and APOE4 transgenic mice. Here, we investigated the effect of APOE4 expression on several aspects of mitochondrial function and network dynamics, including fusion, fission, and mitophagy, specifically in astrocytes. We found that APOE3 and APOE4 astrocytes differ in their mitochondrial dynamics, suggesting that the mitochondria of APOE4 astrocytes exhibit reduced fission and mitophagy. APOE4 astrocytes also show impaired mitochondrial function. Importantly, the autophagy inducer rapamycin enhanced mitophagy and improved mitochondrial functioning in APOE4 astrocytes. Collectively, the results demonstrate that APOE4 expression is associated with altered mitochondrial dynamics, which might lead to impaired mitochondrial function in astrocytes. This, in turn, may contribute to the pathological effects of APOE4 in Alzheimer’s disease.

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“…Mitochondrial morphology, connectivity, and distribution vary greatly within and between cells in different tissues (Collins et al., 2002, Glancy et al., 2015, Woods, 2017). Here, we describe a conserved mitochondrial distribution in exocrine glands, which includes a prominent mitochondrial belt within 2 μm of the basolateral membrane and a subset of mitochondria dispersed in the cytosol (Figures 2 and S1).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Populations Exhibit Differential Dynamic Responses to Increased Energy Demand during Exocytosis In Vivo

et al. 2019

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SummaryMitochondria are dynamic organelles undergoing fission, fusion, and translocation. These processes have been studied in cultured cells; however, little is known about their regulation in cells within tissues in vivo. We applied four-dimensional intravital microscopy to address this in secretory cells of the salivary gland. We found that mitochondria are organized in two populations: one juxtaposed to the basolateral plasma membrane and the other dispersed in the cytosol. Under basal conditions, central mitochondria exhibit microtubule-dependent motility and low fusion rate, whereas basolateral mitochondria are static and display high fusion rate. Increasing cellular energy demand by β-adrenergic stimulation of regulated exocytosis selectively enhanced motility and fusion of central mitochondria. Inhibition of microtubule polymerization led to inhibition of central mitochondrial motility and fusion and a marked reduction in exocytosis. This study reveals a conserved heterogeneity in mitochondrial positioning and dynamics in exocrine tissues that may have fundamental implications in organ pathophysiology.

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Mitochondrial Heterogeneity: Evaluating Mitochondrial Subpopulation Dynamics in Stem Cells

Cited by 43 publications

References 61 publications

Drp1 widely, yet heterogeneously distributes in mice central nervous system

Drp1 widely, yet heterogeneously distributes in mice central nervous system

Altered mitochondrial dynamics and function in APOE4-expressing astrocytes

Mitochondrial Populations Exhibit Differential Dynamic Responses to Increased Energy Demand during Exocytosis In Vivo

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