Enhancement of mitochondrial calcium uptake is cardioprotective against maladaptive hypertrophy by retrograde signaling uptuning Akt.

Regulation of mitochondrial Ca uptake is critical in cardiac adaptation to chronic stressors. Abnormalities in Ca handling, including mitochondrial uptake mechanisms, have been implicated in pathological heart hypertrophy. Enhancing mitochondrial Ca uniporter (MCU) expression has been suggested to interfere with maladaptive development of heart failure.

Neurotoxic Effect of Doxorubicin Treatment on Cardiac Sympathetic Neurons.

Doxorubicin (DOXO) remains amongst the most commonly used anti-cancer agents for the treatment of solid tumors, lymphomas, and leukemias. However, its clinical use is hampered by cardiotoxicity, characterized by heart failure and arrhythmias, which may require chemotherapy interruption, with devastating consequences on patient survival and quality of life. Although the adverse cardiac effects of DOXO are consolidated, the underlying mechanisms are still incompletely understood.

Nerve growth factor transfer from cardiomyocytes to innervating sympathetic neurons activates TrkA receptors at the neuro-cardiac junction.

Sympathetic neurons densely innervate the myocardium with non-random topology and establish structured contacts (i.e. neuro-cardiac junctions, NCJ) with cardiomyocytes, allowing synaptic intercellular communication.

Neurohumoral Cardiac Regulation: Optogenetics Gets Into the Groove.

The cardiac autonomic nervous system (ANS) is the main modulator of heart function, adapting contraction force, and rate to the continuous variations of intrinsic and extrinsic environmental conditions. While the parasympathetic branch dominates during rest-and-digest sympathetic neuron (SN) activation ensures the rapid, efficient, and repeatable increase of heart performance, e.g.

Increased susceptibility to Ca(2+)-induced permeability transition and to cytochrome c release in rat heart mitochondria with aging: effect of melatonin.

Aging is associated with a decline of cardiac function. The mitochondrial permeability transition (MPT) may be a factor in cardiac dysfunction associated with aging. We investigated the effect of aging and long-term treatment with melatonin (approximately 10 mg/kg b.

Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening.

Melatonin, a well-known antioxidant, has been shown to protect against ischemia-reperfusion myocardial damage. Mitochondrial permeability transition pore (MPTP) opening is an important event in cardiomyocyte cell death occurring during ischemia-reperfusion and therefore a possible target for cardioprotection. In the present study, we tested the hypothesis that melatonin could protect heart against ischemia-reperfusion injury by inhibiting MPTP opening.

Melatonin inhibits cardiolipin peroxidation in mitochondria and prevents the mitochondrial permeability transition and cytochrome c release.

Cardiolipin oxidation is emerging as an important factor in mitochondrial dysfunction as well as in the initial phase of the apoptotic process. We have previously shown that exogenously added peroxidized cardiolipin sensitizes mitochondria to Ca(2+)-induced mitochondrial permeability transition (MPT) pore opening and promotes the release of cytochrome c. In this work, the effects of intramitochondrial cardiolipin peroxidation on Ca(2+)-induced MPT and on the cytochrome c release from mitochondria were studied.

Mitochondrial complex I dysfunction in rat heart with aging: critical role of reactive oxygen species and cardiolipin.

Reactive oxygen species (ROS) are considered a key factor in the heart aging process. Mitochondrial respiration is an important site of ROS generation and a potential contributor to heart functional changes with aging. We have examined the effects of aging on various parameters related to mitochondrial bioenergetics in rat heart, such as complex I activity, oxygen consumption, membrane potential, ROS production, and cardiolipin content and oxidation.