In Vivo Tissue-wide Synchronization of Mitochondrial Metabolic Oscillations

Porat-Shliom, Natalie; Chen, Yun; Tora, Muhibullah S; Shitara, Akiko; Masedunskas, Andrius; Weigert, Roberto

doi:10.1016/j.celrep.2014.09.022

Cited by 38 publications

(39 citation statements)

References 47 publications

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“…It is also worth mentioning that recently metabolic oscillations in cells with a period of approximately 10 to 12 s, were measured in vivo [102] which is many orders of magnitude slower than any AC electric field effects discussed here. Hence, it is safe to assume that there is a very unlikely possibility of electric field effects in the 100 kHz range to interfere with cellular metabolism.…”

Section: Ac Electric Field Effects On Subcellular Structuresmentioning

confidence: 88%

An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields

Tuszyński

Wenger

Friesen

et al. 2016

IJERPH

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Long-standing research on electric and electromagnetic field interactions with biological cells and their subcellular structures has mainly focused on the low- and high-frequency regimes. Biological effects at intermediate frequencies between 100 and 300 kHz have been recently discovered and applied to cancer cells as a therapeutic modality called Tumor Treating Fields (TTFields). TTFields are clinically applied to disrupt cell division, primarily for the treatment of glioblastoma multiforme (GBM). In this review, we provide an assessment of possible physical interactions between 100 kHz range alternating electric fields and biological cells in general and their nano-scale subcellular structures in particular. This is intended to mechanistically elucidate the observed strong disruptive effects in cancer cells. Computational models of isolated cells subject to TTFields predict that for intermediate frequencies the intracellular electric field strength significantly increases and that peak dielectrophoretic forces develop in dividing cells. These findings are in agreement with in vitro observations of TTFields’ disruptive effects on cellular function. We conclude that the most likely candidates to provide a quantitative explanation of these effects are ionic condensation waves around microtubules as well as dielectrophoretic effects on the dipole moments of microtubules. A less likely possibility is the involvement of actin filaments or ion channels.

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Section: Ac Electric Field Effects On Subcellular Structuresmentioning

confidence: 88%

An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields

Tuszyński

Wenger

Friesen

et al. 2016

IJERPH

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“…Reactive oxygen species (Aon et al , 2004) and gap junctions (Porat-Shliom et al , 2014) control the synchronization of mitochondrial activity, the oscillations were confirmed by intravital microscopy in living animals (Porat-Shliom et al , 2014) These oscillations were found to disappear with interruption of circulation, inhibiting complex I, and by scavenging ROS. However, they persist but are not coordinated when carbenoxolone, a gap junction inhibitor, is administered.…”

Section: The Mitochondrial Theory Of Agingmentioning

confidence: 89%

“…Recent reports have suggested that mitochondria undergo rapid and constitutive metabolic oscillations in a coordinated manner in individual cells as well as in supracellular networks in the tissue (Porat-Shliom et al , 2014). Reactive oxygen species (Aon et al , 2004) and gap junctions (Porat-Shliom et al , 2014) control the synchronization of mitochondrial activity, the oscillations were confirmed by intravital microscopy in living animals (Porat-Shliom et al , 2014) These oscillations were found to disappear with interruption of circulation, inhibiting complex I, and by scavenging ROS.…”

Section: The Mitochondrial Theory Of Agingmentioning

confidence: 99%

Mitochondrial function in hypoxic ischemic injury and influence of aging

Ham

Raju

2017

Progress in Neurobiology

282

205

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Mitochondria are a major target in hypoxic/ischemic injury. Mitochondrial impairment increases with age leading to dysregulation of molecular pathways linked to mitochondria. The perturbation of mitochondrial homeostasis and cellular energetics worsens outcome following hypoxic-ischemic insults in elderly individuals. In response to acute injury conditions, cellular machinery relies on rapid adaptations by modulating posttranslational modifications. Therefore, post-translational regulation of molecular mediators such as hypoxia-inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), c-MYC, SIRT1 and AMPK play a critical role in the control of the glycolytic-mitochondrial energy axis in response to hypoxic-ischemic conditions. The deficiency of oxygen and nutrients leads to decreased energetic reliance on mitochondria, promoting glycolysis. The combination of pseudohypoxia, declining autophagy, and dysregulation of stress responses with aging adds to impaired host response to hypoxic-ischemic injury. Furthermore, intermitochondrial signal propagation and tissue wide oscillations in mitochondrial metabolism in response to oxidative stress are emerging as vital to cellular energetics. Recently reported intercellular transport of mitochondria through tunneling nanotubes also play a role in the response to and treatments for ischemic injury. In this review we attempt to provide an overview of some of the molecular mechanisms and potential therapies involved in the alteration of cellular energetics with aging and injury with a neurobiological perspective.

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“…This could be accomplished by extending our method from the organ level to the cellular level to visualize local Ca 2þ responses. Subcellular events in salivary acinar cells, including membrane trafficking, cytoskeletal organization, and mitochondrial metabolism, were visualized successfully by the Weigert group, using confocal and two-photon microscopy [52][53][54]. These methods might be applicable for visualizing subcellular Ca 2þ responses in live animals.…”

Section: Prospectivementioning

confidence: 98%