Mitochondrialand: What Will Come Next?

Pizzo, Paola; Pozzan, Tullio

doi:10.1093/function/zqab073

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…Following this provocative report [ 59 ], several publications confirmed that some cells are capable of interacting directly with other cells via tubular membranous structures named “tunneling nanotubes” (TNT), capable of creating large membranous pores by fusing with the plasma membrane of the receiving cell and transferring cytoplasmic organelles and large as mitochondria; rev. in [ 60 , 61 , 62 , 63 , 64 ] among others. Evidence of tunneling nanotubes finally confirmed our data suggesting that some neighboring cells can communicate directly with each other via membrane pores [ 53 ].…”

Section: Direct Cell-cell Communication Via Membrane Poresmentioning

confidence: 99%

“…A recent commentary [ 64 ] updated the present trends in mitochondrial research to three areas: (1) the causal role of mitochondrial dysfunction in several neurodegenerative ailments, such as Parkinson’s and Alzheimer’s disease; (2) the control of Ca 2+ milIeu in selected intracellular micro-domains, changing intracellular responses; and (3) microvesicle (mV) or TNT-mediated transfer of mitochondria within different cells and tissues, of healthy or of degenerated mitochondria, as a mechanism of functional renewal in diseased cells, or fostering propagation of cell distress or pathology, such as in metastatic cancer evolution.…”

Section: Tnt or Cytonemes A New Concept For A Novel Long-rangementioning

confidence: 99%

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Direct Cell-Cell Communication via Membrane Pores, Gap Junction Channels, and Tunneling Nanotubes: Medical Relevance of Mitochondrial Exchange

Eugenin

Camporesi

Peracchia

2022

IJMS

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The history of direct cell-cell communication has evolved in several small steps. First discovered in the 1930s in invertebrate nervous systems, it was thought at first to be an exception to the “cell theory”, restricted to invertebrates. Surprisingly, however, in the 1950s, electrical cell-cell communication was also reported in vertebrates. Once more, it was thought to be an exception restricted to excitable cells. In contrast, in the mid-1960s, two startling publications proved that virtually all cells freely exchange small neutral and charged molecules. Soon after, cell-cell communication by gap junction channels was reported. While gap junctions are the major means of cell-cell communication, in the early 1980s, evidence surfaced that some cells might also communicate via membrane pores. Questions were raised about the possible artifactual nature of the pores. However, early in this century, we learned that communication via membrane pores exists and plays a major role in medicine, as the structures involved, “tunneling nanotubes”, can rescue diseased cells by directly transferring healthy mitochondria into compromised cells and tissues. On the other hand, pathogens/cancer could also use these communication systems to amplify pathogenesis. Here, we describe the evolution of the discovery of these new communication systems and the potential therapeutic impact on several uncurable diseases.

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Section: Direct Cell-cell Communication Via Membrane Poresmentioning

confidence: 99%

Section: Tnt or Cytonemes A New Concept For A Novel Long-rangementioning

confidence: 99%

Direct Cell-Cell Communication via Membrane Pores, Gap Junction Channels, and Tunneling Nanotubes: Medical Relevance of Mitochondrial Exchange

Eugenin

Camporesi

Peracchia

2022

IJMS

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Cellular Bioenergetics: Experimental Evidence for Alcohol-induced Adaptations

Simon

Molina

2022

Function

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At-risk alcohol use is associated with multisystemic effects and end-organ injury, and significantly contributes to global health burden. Several alcohol-mediated mechanisms have been identified, with bioenergetic maladaptation gaining credence as an underlying pathophysiological mechanism contributing to cellular injury. This evidence-based review focuses on the current knowledge of alcohol-induced bioenergetic adaptations in metabolically active tissues: liver, cardiac and skeletal muscle, pancreas, and brain. Alcohol metabolism itself significantly interferes with bioenergetic pathways in tissues, particularly the liver. Alcohol decreases states of respiration in the electron transport chain, and activity and expression of respiratory complexes, with a net effect to decrease ATP content. In addition, alcohol dysregulates major metabolic pathways including glycolysis, the tricarboxylic acid (TCA) cycle, and fatty acid oxidation. These bioenergetic alterations are influenced by alcohol-mediated changes in mitochondrial morphology, biogenesis, and dynamics. The review highlights similarities and differences in bioenergetic adaptations according to tissue type, pattern of (acute vs. chronic) alcohol use, and energy substrate availability. The compromised bioenergetics synergizes with other critical pathophysiological mechanisms including increased oxidative stress and accelerates cellular dysfunction, promoting senescence, programmed cell death, and end-organ injury.

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Supercomplex supercomplexes: Raison d’etre and functional significance of supramolecular organization in oxidative phosphorylation

Nath

2022

Biomolecular Concepts

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Following structural determination by recent advances in electron cryomicroscopy, it is now well established that the respiratory Complexes I–IV in oxidative phosphorylation (OXPHOS) are organized into supercomplexes in the respirasome. Nonetheless, the reason for the existence of the OXPHOS supercomplexes and their functional role remains an enigma. Several hypotheses have been proposed for the existence of these supercomplex supercomplexes. A commonly-held view asserts that they enhance catalysis by substrate channeling. However, this – and other views – has been challenged based on structural and biophysical information. Hence, new ideas, concepts, and frameworks are needed. Here, a new model of energy transfer in OXPHOS is developed on the basis of biochemical data on the pure competitive inhibition of anionic substrates like succinate by the classical anionic uncouplers of OXPHOS (2,4-dinitrophenol, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, and dicoumarol), and pharmacological data on the unique site-selective, energy-linked inhibition of energy conservation pathways in mitochondria induced by the guanidine derivatives. It is further found that uncouplers themselves are site-specific and exhibit differential selectivity and efficacy in reversing the inhibition caused by the Site 1/Complex I or Site 2/Complexes II–III-selective guanidine derivatives. These results lead to new vistas and sufficient complexity in the network of energy conservation pathways in the mitochondrial respiratory chain that necessitate discrete points of interaction with two classes of guanidine derivatives and uncoupling agents and thereby separate and distinct energy transfer pathways between Site 1 and Site 2 and the intermediate that energizes adenosine triphosphate (ATP) synthesis by Complex V. Interpretation based on Mitchell’s single-ion chemiosmotic theory that postulates only a single energy pool is inadequate to rationalize the data and account for the required complexity. The above results and available information are shown to be explained by Nath’s two-ion theory of energy coupling and ATP synthesis, involving coupled movement of succinate anions and protons, along with the requirement postulated by the theory for maintenance of homeostasis and ion translocation across the energy-transducing membrane of both succinate monoanions and succinate dianions by Complexes I–V in the OXPHOS supercomplexes. The new model of energy transfer in mitochondria is mapped onto the solved structures of the supercomplexes and integrated into a consistent model with the three-dimensional electron microscope computer tomography visualization of the internal structure of the cristae membranes in mammalian mitochondria. The model also offers valuable insights into diseased states induced in type 2 diabetes and especially in Alzheimer’s and other neurodegenerative diseases that involve mitochondrial dysfunction.

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Mitochondrialand: What Will Come Next?

Cited by 3 publications

References 10 publications

Direct Cell-Cell Communication via Membrane Pores, Gap Junction Channels, and Tunneling Nanotubes: Medical Relevance of Mitochondrial Exchange

Direct Cell-Cell Communication via Membrane Pores, Gap Junction Channels, and Tunneling Nanotubes: Medical Relevance of Mitochondrial Exchange

Cellular Bioenergetics: Experimental Evidence for Alcohol-induced Adaptations

Supercomplex supercomplexes: Raison d’etre and functional significance of supramolecular organization in oxidative phosphorylation

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