PRKN/parkin-mediated mitophagy is induced by the probiotics and .

Mitochondrial impairment is a hallmark feature of neurodegenerative disorders, such as Parkinson disease, and PRKN/parkin-mediated mitophagy serves to remove unhealthy mitochondria from cells. Notably, probiotics are used to alleviate several symptoms of Parkinson disease including impaired locomotion and neurodegeneration in preclinical studies and constipation in clinical trials. There is some evidence to suggest that probiotics can modulate mitochondrial quality control pathways.

Review: A history and perspective of mitochondria in the context of anoxia tolerance.

Symbiosis is found throughout nature, but perhaps nowhere is it more fundamental than mitochondria in all eukaryotes. Since mitochondria were discovered and mechanisms of oxygen reduction characterized, an understanding gradually emerged that these organelles were involved not just in the combustion of oxygen, but also in the sensing of oxygen. While multiple hypotheses exist to explain the mitochondrial involvement in oxygen sensing, key elements are developing that include potassium channels and reactive oxygen species.

Oxygen-sensitive interneurons exhibit increased activity and GABA release during ROS scavenging in the cerebral cortex of the western painted turtle.

The western painted turtle () has the unique ability of surviving several months in the absence of oxygen, which is termed anoxia. One major protective strategy that the turtle employs during anoxia is a reduction in neuronal electrical activity, which may result from a natural reduction in reactive oxygen species (ROS). We previously linked a reduction in ROS levels to an increase in γ-amino butyric acid (GABA) receptor currents.

Mitochondrial matrix pH acidifies during anoxia and is maintained by the FF-ATPase in anoxia-tolerant painted turtle cortical neurons.

The western painted turtle () can survive extended periods of anoxia via a series of mechanisms that serve to reduce its energetic needs. Central to these mechanisms is the response of mitochondria, which depolarize in response to anoxia in turtle pyramidal neurons due to an influx of K. It is currently unknown how mitochondrial matrix pH is affected by this response and we hypothesized that matrix pH acidifies during anoxia due to increased K/H exchanger activity.

Phosphorylation of the mitochondrial ATP-sensitive potassium channel occurs independently of PKCε in turtle brain.

Neurons from the western painted turtle (Chrysemys picta bellii) are remarkably resilient to anoxia. This is partly due to a reduction in the permeability of excitatory glutamatergic ion channels, initiated by mitochondrial ATP-sensitive K(+) (mK(+)ATP) channel activation. The aim of this study was to determine if: 1) PKCε, a kinase associated with hypoxic stress tolerance, is more highly expressed in turtle brain than the anoxia-intolerant rat brain; 2) PKCε translocates to the mitochondrial membrane during anoxia; 3) PKCε modulates mK(+)ATP channels at the Thr-224 phosphorylation site on the Kir6.

Scavenging ROS dramatically increase NMDA receptor whole-cell currents in painted turtle cortical neurons.

Oxygen deprivation triggers excitotoxic cell death in mammal neurons through excessive calcium loading via over-activation of N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This does not occur in the western painted turtle, which overwinters for months without oxygen. Neurological damage is avoided through anoxia-mediated decreases in NMDA and AMPA receptor currents that are dependent upon a modest rise in intracellular Ca(2+) concentrations ([Ca(2+)]i) originating from mitochondria.

Anoxia-mediated calcium release through the mitochondrial permeability transition pore silences NMDA receptor currents in turtle neurons.

Mammalian neurons are anoxia sensitive and rapidly undergo excitotoxic cell death when deprived of oxygen, mediated largely by Ca(2+) entry through over-activation of N-methyl-d-aspartate receptors (NMDARs). This does not occur in neurons of the anoxia-tolerant western painted turtle, where a decrease in NMDAR currents is observed with anoxia. This decrease is dependent on a modest rise in cytosolic [Ca(2+)] ([Ca(2+)]c) that is mediated by release from the mitochondria.