Automatic Morphological Subtyping Reveals New Roles of Caspases in Mitochondrial Dynamics

Peng, Jyh Ying; Lin, Chung Chih; Chen, Yen Jen; Kao, Lung‐Sen; Liu, Young Chau; Chou, Chung Chien; Huang, Yi Hung; Chang, Fang Rong; Wu, Yang Chang; Tsai, Yuh-Show; Hsu, Chun Nan

doi:10.1371/journal.pcbi.1002212

Cited by 115 publications

(115 citation statements)

References 44 publications

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“…The latter study as well as others (e.g. [249]) demonstrated that additional mitochondrial subtyping (i.e. using more than the three categories described above) may also be applied to account for differences in shape and appearance.…”

Section: Interpretation Of Quantitative Data For Mitochondrial Morphomentioning

confidence: 77%

Regulation and Quantification of Cellular Mitochondrial Morphology and Content

Tronstad¹,

Nooteboom²,

Nilsson³

et al. 2014

CPD

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Running title: Regulation and quantification of mitochondrial morphology and content. Word count: 15,454 (total)Characters: 107,091 (including spaces); 92,067 (excluding spaces) Keywords: mitochondrial biogenesis, mitochondrial dynamics, mitochondrial degradation, living cells, TMRM, microscopy, segmentation, image analysis.Page 2 of 37 ABSTRACTMitochondria play a key role in signal transduction, redox homeostasis and cell survival, which extends far beyond their classical functioning in ATP production and energy metabolism. In living cells, mitochondrial content ("mitochondrial mass") depends on the cell-controlled balance between mitochondrial biogenesis and degradation. These processes are intricately linked to changes in net mitochondrial morphology and spatiotemporal positioning ("mitochondrial dynamics"), which are governed by mitochondrial fusion, fission and motility. It is becoming increasingly clear that mitochondrial mass and dynamics, as well as its ultrastructure and volume, are mechanistically linked to mitochondrial function and the cell. This means that proper quantification of mitochondrial morphology and content is of prime importance in understanding mitochondrial and cellular physiology in health and disease. This review first presents how cellular mitochondrial content is regulated at the level of mitochondrial biogenesis, degradation and dynamics. Next we discuss how mitochondrial dynamics and content can be analyzed with a special emphasis on quantitative live-cell microscopy strategies.

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Section: Interpretation Of Quantitative Data For Mitochondrial Morphomentioning

confidence: 77%

Regulation and Quantification of Cellular Mitochondrial Morphology and Content

Tronstad¹,

Nooteboom²,

Nilsson³

et al. 2014

CPD

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“…Another intriguing computational approach [24] involves automated subtyping of mitochondrial morphology. We have also attempted to employ the MicroP software written by the authors for our experimental needs, however, it was similarly very difficult for us to learn due to the technical (computational knowledge) needed.…”

Section: Discussionmentioning

confidence: 99%

An Improved Quantitative Approach for the Assessment of Mitochondrial Fragmentation in Chemoresistant Ovarian Cancer Cells

et al. 2013

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Mitochondrial fission is a process that involves cleavage of mitochondria into smaller fragments and is regulated by the GTPase Dynamin-related protein 1 (Drp1). Higher levels of mitochondrial fission are associated with the induction of apoptosis in cancer cells. However, current methods to accurately quantify mitochondrial fission in order to compare therapeutics that target this process are often ambiguous or rely on subjective assessment. Mitochondria are also prone to aggregation, making accurate analysis difficult. Here we describe an improved approach for the quantification of mitochondrial fragmentation involving several differences from currently existing methods. Cells are first subjected to cytological centrifugation, which reduces cellular z-axis height and disperses individual mitochondria for easier observation. Three commercially available fluorescence analysis tools are then applied to disambiguate remaining mitochondrial clusters that require further inspection. Finally, cut-off scoring is applied, which can be tailored to individual cell type. The resultant approach allows for the efficient and objective assessment of mitochondrial fragmentation in response to treatment. We applied this technique to an experimental question involving chemosensitive and chemoresistant ovarian cancer (OVCA) cells. Cisplatin and the phytochemical piperlongumine were found to induce both mitochondrial fission and apoptosis in chemosensitive cells, while only piperlongumine was able to elicit these cellular responses in chemoresistant cells. Piperlongumine-induced apoptosis appeared to be mediated by Drp1-dependent mitochondrial fission since the apoptotic response was attenuated by the presence of the Drp1 inhibitor mDivi-1. Our study provides groundwork for a more objective approach to the quantification of mitochondrial fragmentation, and sheds further light on a potential mechanism of action for piperlongumine in the treatment of chemoresistant OVCA.

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“…“compact” versus “branched”, “non-tubular” versus “tubular”) (Vowinckel et al, 2015). When consensus clustering was applied to automatically define morphological subtypes in mitochondrial images, a total of 19 distinct morphological clusters were identified, suggesting that mitochondrial shape complexity is under-appreciated even when a single cell type is considered (Peng et al, 2011). The diversity in mitochondrial morphology may be far greater considering the extent to which mitochondria are specialized between the various cell types (Vafai and Mootha, 2012).…”

Section: Descriptions Of Mitochondrial Morphologymentioning

confidence: 99%

Connecting mitochondrial dynamics and life-or-death events via Bcl-2 family proteins

Aouacheria

Baghdiguian

Lamb

et al. 2017

Neurochemistry International

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The morphology of a population of mitochondria is the result of several interacting dynamical phenomena, including fission, fusion, movement, elimination and biogenesis. Each of these phenomena is controlled by underlying molecular machinery, and when defective can cause disease. New understanding of the relationships between form and function of mitochondria in health and disease is beginning to be unraveled on several fronts. Studies in mammals and model organisms have revealed that mitochondrial morphology, dynamics and function appear to be subject to regulation by the same proteins that regulate apoptotic cell death. One protein family that influences mitochondrial dynamics in both healthy and dying cells is the Bcl-2 protein family. Connecting mitochondrial dynamics with life-death pathway forks may arise from the intersection of Bcl-2 family proteins with the proteins and lipids that determine mitochondrial shape and function. Bcl-2 family proteins also have multifaceted influences on cells and mitochondria, including calcium handling, autophagy and energetics, as well as the subcellular localization of mitochondrial organelles to neuronal synapses. The remarkable range of physical or functional interactions by Bcl-2 family proteins is challenging to assimilate into a cohesive understanding. Most of their effects may be distinct from their direct roles in apoptotic cell death and are particularly apparent in the nervous system. Dual roles in mitochondrial dynamics and cell death extend beyond BCL-2 family proteins. In this review, we discuss many processes that govern mitochondrial structure and function in health and disease, and how Bcl-2 family proteins integrate into some of these processes.

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Automatic Morphological Subtyping Reveals New Roles of Caspases in Mitochondrial Dynamics

Cited by 115 publications

References 44 publications

Regulation and Quantification of Cellular Mitochondrial Morphology and Content

Regulation and Quantification of Cellular Mitochondrial Morphology and Content

An Improved Quantitative Approach for the Assessment of Mitochondrial Fragmentation in Chemoresistant Ovarian Cancer Cells

Connecting mitochondrial dynamics and life-or-death events via Bcl-2 family proteins

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