Effect of acriflavin on the mitochondria of the rat

Resumen La administración de acriflavina provoca la aparición de un elevado número de mitocondrias con filamentos de ADN en el hígado, riñón y miocardio de la rata. Sobre la base de este hecho se sugiere que la acriflavina inhibe la reproducción del ADN mitocondrial, haciéndolo visible a nivel ultraestructural.     

Rapid staining of mitochondria

Riassunto Viene descritta una nuova semplice tecnica per la colorazione rapida dei mitocondri nelle sezioni di tessuti: i pezzi devono essere fissati in formalina, le fettine, dopo sparaffinamento, vengono immerse in una soluzione calda (60°C) di acido cloridrico normale per 3 min e poi colorate con fucsina acida (1%) per 30 sec e con verde luce (1%) per 1–3 min. I mitocondri risaltano intensamente colorati in rosso con una sottile parete colorata in verde.     

Melatonin,mitochondria, and the skin

The skin being a protective barrier between external and internal (body) environments has the sensory and adaptive capacity to maintain local and global body homeostasis in response to noxious factors. An important part of the skin response to stress is its ability for melatonin synthesis and subsequent metabolism through the indolic and kynuric pathways. Indeed, melatonin and its metabolites have emerged as indispensable for physiological skin functions and for effective protection of a cutaneous homeostasis from hostile environmental factors. Moreover, they attenuate the pathological processes including carcinogenesis and other hyperproliferative/inflammatory conditions. Interestingly, mitochondria appear to be a central hub of melatonin metabolism in the skin cells. Furthermore, substantial evidence has accumulated on the protective role of the melatonin against ultraviolet radiation and the attendant mitochondrial dysfunction. Melatonin and its metabolites appear to have a modulatory impact on mitochondrion redox and bioenergetic homeostasis, as well as the anti-apoptotic effects. Of note, some metabolites exhibit even greater impact than melatonin alone. Herein, we emphasize that melatonin–mitochondria axis would control integumental functions designed to protect local and perhaps global homeostasis. Given the phylogenetic origin and primordial actions of melatonin, we propose that the melatonin-related mitochondrial functions represent an evolutionary conserved mechanism involved in cellular adaptive response to skin injury and repair.     

Tyrosine phosphatase activity in mitochondria: presence of Shp-2 phosphatase in mitochondria

Tyrosine phosphorylation by unidentified enzymes has been observed in mitochondria, with recent evidence indicating that non-receptorial tyrosine kinases belonging to the Src family, which represent key players in several transduction pathways, are constitutively present in mitochondria. The extent of protein phosphorylation reflects a coordination balance between the activities of specific kinases and phophatases. The present study demonstrates that purified rat brain mitochondria possess endogenous tyrosine phosphatase activity. Mitochondrial phosphatases were found to be capable of dephosphorylating different exogenous substrates, including paranitrophenylphosphate, ³²P-poly(Glu-Tyr)_4:1 and ³²P-angiotensin. These activities are strongly inhibited by peroxovanadate, a well-known inhibitor of tyrosine phosphatases, but not by inhibitors of alkali or Ser/Thr phosphatases, and mainly take place in the intermembrane space and outer mitochondrial membrane. Using a combination of approaches, we identified the tyrosine phosphatase Shp-2 in mitochondria. Shp-2 plays a crucial role in a number of intracellular signalling cascades and is probably involved in several human diseases. It thus represents the first tyrosine phosphatase shown to be present in mitochondria.Received 17 May 2004; received after revision 20 July 2004; accepted 26 July 2004     

Melatonin transport into mitochondria

Melatonin is a well-known, nighttime-produced indole found in bacteria, eukaryotic unicellulars, animals or vascular plants. In vertebrates, melatonin is the major product of the pineal gland, which accounts for its increase in serum during the dark phase, but it is also produced by many other organs and cell types. Such a wide distribution is consistent with its multiple and well-described functions which include from the circadian regulation and adaptation to seasonal variations to immunomodulatory and oncostatic actions in different types of tumors. The discovery of its antioxidant properties in the early 1990s opened a new field of potential protective functions in multiple tissues. A special mention should be made regarding the nervous system, where the indole is considered a major neuroprotector. Furthermore, mitochondria appear as one of the most important targets for the indole’s protective actions. Melatonin’s mechanisms of action vary from the direct molecular interaction with free radicals (free radical scavenger) to the binding to membrane (MLT1A and MLT1B) or nuclear receptors (RZR/RORα). Receptor binding has been associated with some, but not all of the indole functions reported to date. Recently, two new mechanisms of cellular uptake involving the facilitative glucose transporters GLUT/SLC2A and the proton-driven oligopeptide transporter PEPT1/2 have been reported. Here we discuss the potential importance that these newly discovered transport systems could have in determining the actions of melatonin, particularly in the mitochondria. We also argue the relative importance of passive diffusion vs active transport in different parts of the cell.     

Abnormal mitochondria in retinoblastoma

Summary In examination of six retinoblastoma tumor specimens, bizzare mitochondria were often found. Some are irregular forms with focal expansion and constrictions. Occasionally, a portion of the mitochondria forms rings. Branching mitochondria are also seen. Other striking features of the mitochondria from tumor cells are the alteration of cristae. Dense bodies are also occasionally observed within the mitochondria. Morphological modifications of the mitochondria may be as results of pathological conditions of the tumor cells.     

Revisiting the role of mitochondria in spinal muscular atrophy

Cellular and Molecular Life Sciences - Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease of variable clinical severity that is caused by mutations in the survival motor...     

Melatonin,mitochondria, and the metabolic syndrome

A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.     

Melatonin,mitochondria, and the cancer cell

The long-recognized fact that oxidative stress within mitochondria is a hallmark of mitochondrial dysfunction has stimulated the development of mitochondria-targeted antioxidant therapies. Melatonin should be included among the pharmacological agents able to modulate mitochondrial functions in cancer, given that a number of relevant melatonin-dependent effects are triggered by targeting mitochondrial functions. Indeed, melatonin may modulate the mitochondrial respiratory chain, thus antagonizing the cancer highly glycolytic bioenergetic pathway of cancer cells. Modulation of the mitochondrial respiratory chain, together with Ca²⁺ release and mitochondrial apoptotic effectors, may enhance the spontaneous or drug-induced apoptotic processes. Given that melatonin may efficiently counteract the Warburg effect while stimulating mitochondrial differentiation and mitochondrial-based apoptosis, it is argued that the pineal neurohormone could represent a promising new perspective in cancer treatment strategy.     

Investigations on the turnover of adrenocortical mitochondria. VII. Effects of ACTH on the half-life of mitochondria from the zona reticularis of the rat adrenal cortex

Summary The half-life of mitochondria from the zona reticularis of the rat adrenal was calculated by determining the radioactivity decay curves of the mitochondrial compartment of 3H-thymidine-injected animals, using autoradiographic methods. ACTH was found to enhance significantly the half-life of the organelles.Acknowledgment. We wish to thank Miss A. Coi and Mr G. Gottardo for the skilled techical assistance. This work was partly supported by a contract with the CNR (No. 74.00226.04/115.3439).     

Antigen-distribution in rat liver mitochondria

Riassunto I mitocondri di fegato di ratto possiedono almeno tre gruppi di antigeni, dei quali uno è esclusivamente legato alle membrane mitocondriali, uno è presente nella frazione solubile in 0,3% desossicolato di sodio ed un altro, che, sebbene principalmente localizzato nelle membrane, è anche dimostrabile nella frazione desossicolato solubile.     

Abnormal mitochondria in retinoblastoma.

In examination of six retinoblastoma tumor specimens, bizzare mitochondria were often found. Some are irregular forms with focal expansion and constrictions. Occasionally, a portion of the mitochondria forms rings. Branching mitochondria are also seen. Other striking features of the mitochondria from tumor cells are the alternation of cristae. Dense bodies are also occasionally observed within the mitochondria. Morphological modifications of the mitochondria may be as results of pathological conditions of the tumor cells.     

Melatonin,mitochondria and hypertension

Melatonin, due to its multiple means and mechanisms of action, plays a fundamental role in the regulation of the organismal physiology by fine tunning several functions. The cardiovascular system is an important site of action as melatonin regulates blood pressure both by central and peripheral interventions, in addition to its relation with the renin–angiotensin system. Besides, the systemic management of several processes, melatonin acts on mitochondria regulation to maintain a healthy cardiovascular system. Hypertension affects target organs in different ways and cellular energy metabolism is frequently involved due to mitochondrial alterations that include a rise in reactive oxygen species production and an ATP synthesis decrease. The discussion that follows shows the role played by melatonin in the regulation of mitochondrial physiology in several levels of the cardiovascular system, including brain, heart, kidney, blood vessels and, particularly, regulating the renin–angiotensin system. This discussion shows the putative importance of using melatonin as a therapeutic tool involving its antioxidant potential and its action on mitochondrial physiology in the cardiovascular system.     

Regulated protein degradation in mitochondria

Various adenosine triphosphate (ATP)-dependent proteases were identified within mitochondria which mediate selective mitochondrial protein degradation and fulfill crucial functions in mitochondrial biogenesis. The matrix-localized PIM1 protease, a homologue of theEscherichia coli Lon protease, is required for respiration and maintenance of mitochondrial genome integrity. Degradation of non-native polypeptides by PIM1 protease depends on the chaperone activity of the mitochondrial Hsp70 system, posing intriguing questions about the relation between the proteolytic system and the folding machinery in mitochondria. The mitochondrial inner membrane harbors two ATP-dependent metallopeptidases, them- and thei-AAA protease, which expose their catalytic sites to opposite membrane surfaces and cooperate in the degradation of inner membrane proteins. In addition to its proteolytic activity, them-AAA protease has chaperone-like activity during the assembly of respiratory and ATP-synthase complexes. It constitutes a quality control system in the inner membrane for membrane-embedded protein complexes.     

Effect of continuous illumination on mitochondria of the rat pineal body

Zusammenfassung Die Rattenepiphyse von Tieren, die 30 Tage lang einer ständigen Belichtung von 70 Lux Stärke ausgesetzt worden waren, wurde elektronen-optisch untersucht. Alle Tiere wiesen mitochondriale Veränderungen der Pinealozyten auf. Diese Veränderungen sind vermutlich auf den erhöhten Serotoninstoffwechsel zurückzuführen, der durch die ständige Belichtung induziert wird, da die Kontrolltiere keine derartigen Abartigkeiten zeigten.