Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance.

Eukaryotes employ elaborate mitochondrial quality control (MQC) to maintain the function of the power-generating organelle. Parkinson's disease-associated PINK1 and Parkin actively participate in MQC. However, the signaling events involved are largely unknown.

PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy.

Parkinson's disease genes PINK1 and parkin encode kinase and ubiquitin ligase, respectively. The gene products PINK1 and Parkin are implicated in mitochondrial autophagy, or mitophagy. Upon the loss of mitochondrial membrane potential (ΔΨm), cytosolic Parkin is recruited to the mitochondria by PINK1 through an uncharacterised mechanism - an initial step triggering sequential events in mitophagy.

Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria.

Mutations in Pten-induced kinase 1 (PINK1) are linked to early-onset familial Parkinson's disease (FPD). PINK1 has previously been implicated in mitochondrial fission/fusion dynamics, quality control, and electron transport chain function. However, it is not clear how these processes are interconnected and whether they are sufficient to explain all aspects of PINK1 pathogenesis.

The nitric oxide-cyclic GMP pathway regulates FoxO and alters dopaminergic neuron survival in Drosophila.

Activation of the forkhead box transcription factor FoxO is suggested to be involved in dopaminergic (DA) neurodegeneration in a Drosophila model of Parkinson's disease (PD), in which a PD gene product LRRK2 activates FoxO through phosphorylation. In the current study that combines Drosophila genetics and biochemical analysis, we show that cyclic guanosine monophosphate (cGMP)-dependent kinase II (cGKII) also phosphorylates FoxO at the same residue as LRRK2, and Drosophila orthologues of cGKII and LRRK2, DG2/For and dLRRK, respectively, enhance the neurotoxic activity of FoxO in an additive manner. Biochemical assays using mammalian cGKII and FoxO1 reveal that cGKII enhances the transcriptional activity of FoxO1 through phosphorylation of the FoxO1 S319 site in the same manner as LRRK2.

The loss of PGAM5 suppresses the mitochondrial degeneration caused by inactivation of PINK1 in Drosophila.

PTEN-induced kinase 1 (PINK1), which is required for mitochondrial homeostasis, is a gene product responsible for early-onset Parkinson's disease (PD). Another early onset PD gene product, Parkin, has been suggested to function downstream of the PINK1 signalling pathway based on genetic studies in Drosophila. PINK1 is a serine/threonine kinase with a predicted mitochondrial target sequence and a probable transmembrane domain at the N-terminus, while Parkin is a RING-finger protein with ubiquitin-ligase (E3) activity.

Activation of FoxO by LRRK2 induces expression of proapoptotic proteins and alters survival of postmitotic dopaminergic neuron in Drosophila.

Missense mutations in leucine-rich repeat kinase 2 (LRRK2)/Dardarin gene, the product of which encodes a kinase with multiple domains, are known to cause autosomal dominant late onset Parkinson's disease (PD). In the current study, we report that the gene product LRRK2 directly phosphorylates the forkhead box transcription factor FoxO1 and enhances its transcriptional activity. This pathway was found to be conserved in Drosophila, as the Drosophila LRRK2 homolog (dLRRK) enhanced the neuronal toxicity of FoxO.

Lymphangiogenesis promotes lens destruction and subsequent lens regeneration in the newt eyeball, and both processes can be accelerated by transplantation of dendritic cells.

We examined whether lymphangiogenesis is essential for the process of lens destruction and subsequent remodeling in the newt eye. Lens regeneration was induced by pricking the lens once with a needle through the cornea. The results showed that the formation of the vacuoles which was mediated by lysosomes occurred in the original lens on 8 days after pricking, and histolysis of the lens was induced 24 h later.

Exposure to low-dose X-rays promotes peculiar autophagic cell death in Drosophila melanogaster, an effect that can be regulated by the inducible expression of Hml dsRNA.

We previously reported that to induce an early emergence effect with low-dose X-irradiation in Drosophila, exposure during the prepupae stage is necessary. The present study examined the mechanism by which low-dose radiation rapidly eliminates larval cells and activates the formation of the imaginal discs during metamorphosis. Upon exposure to 0.

Low dose beta-emitter source induces sexual reproduction instead of fragmentation in an earthworm, Enchytraeus japonensis.

We examined whether background radiation, or radiation at a slightly higher level, plays a role in the reproduction of a terrestrial earthworm. Enchytraeus japonensis a recently described terrestrial oligochaete, reproduces asexually by fragmentation and subsequent regeneration. Following radiation exposure in which the worms were subjected to a 32P beta-emitter source at 15 times the background dose rate (4.

Marked depression of time interval between fertilization period and hatching period following exposure to low-dose X-rays in zebrafish.

In recent years there has been growing concern over the stimulating effects of very low-dose X-rays. Our laboratory had observed that zebrafish irradiated with low-dose X-rays tended to emerge earlier than sham controls. This observation led us to quantitatively examine the effects of low-dose X irradiation on a series of stages of development in the zebrafish.

Parental exposure to low-dose X-rays in Drosophila melanogaster induces early emergence in offspring, which can be modulated by transplantation of polar cytoplasm.

In recent years there has been growing concern over the biological effects of low-dose X-rays, but few studies have addressed this issue. Our laboratory had observed flies (Drosophila melanogaster) irradiated with low-dose X-rays tend to emerge earlier than normal flies. This observation led us to quantitatively examine the effects of low-dose X-irradiation on development in the fly.

Terrestrial isopods congregate under a low-level beta-emitter source.

Ionizing radiation is ubiquitous, but very few experiments have investigated the biological effects of the natural background radiation at very low doses (>10 mGy/yr). We examined whether the background radiation, or radiation of a slightly higher level, has a role in evoking changes in behaviors of terrestrial isopods (woodlice). Upon exposure to a source giving 15 times the background level placed at one end of a box, a significant increase in the number of woodlice gathering under the beta-source was observed with time, as compared with the sham control.

Marked depression of radiation-induced emesis in frogs following prior exposure to a brief dose of X-rays.

Acute emesis response to harmful doses of X-rays on frogs (Rana porosa porosa) was examined. Results showed that the number of radioemesis events following exposure to 0.85 Gy was slightly higher than in the sham control animals.