Reproductive regulation of the mitochondrial stress response in Caenorhabditis elegans.

Proteome integrity is fundamental for cellular and organismal homeostasis. The mitochondrial unfolded protein response (UPR), a key component of the proteostasis network, is activated in a non-cell-autonomous manner in response to mitochondrial stress in distal tissues. However, the importance of inter-tissue communication for UPR inducibility under physiological conditions remains elusive.

Assessing polyglutamine tract aggregation in the nematode Caenorhabditis elegans.

Proteome integrity is a prerequisite for cellular functionality and organismal viability. Its compromise is considered an inherent part of the aging process and has been associated with the onset of age-related, neurodegenerative pathologies. Although the molecular underpinnings of protein homeostasis (proteostasis) have been extensively studied, several aspects of its regulation remain elusive.

The interplay between selective types of (macro)autophagy: Mitophagy and xenophagy.

Autophagy is a physiological response, activated by a myriad of endogenous and exogenous cues, including DNA damage, perturbation of proteostasis, depletion of nutrients or oxygen and pathogen infection. Upon sensing those stimuli, cells employ multiple non-selective and selective autophagy pathways to promote fitness and survival. Importantly, there are a variety of selective types of autophagy.

The κ-opioid receptor-induced autophagy is implicated in stress-driven synaptic alterations.

Recent evidence has shown that G protein-coupled receptors (GPCRs) are direct sensors of the autophagic machinery and opioid receptors regulate neuronal plasticity and neurotransmission with an as yet unclarified mechanism. Using and experimental approaches, this study aims to clarify the potential role of autophagy and κ-opioid receptor (κ-OR) signaling in synaptic alterations. We hereby demonstrate that the selective κ-OR agonist U50,488H, induces autophagy in a time-and dose-dependent manner in Neuro-2A cells stably expressing the human κ-OR by upregulating microtubule-associated protein Light Chain 3-II (LC3-II), Beclin 1 and Autophagy Related Gene 5 (ATG5).

Sustained intracellular calcium rise mediates neuronal mitophagy in models of autosomal dominant optic atrophy.

Mitochondrial dysfunction and mitophagy are often hallmarks of neurodegenerative diseases such as autosomal dominant optic atrophy (ADOA) caused by mutations in the key mitochondrial dynamics protein optic atrophy 1 (Opa1). However, the second messengers linking mitochondrial dysfunction to initiation of mitophagy remain poorly characterized. Here, we show in mammalian and nematode neurons that Opa1 mutations trigger Ca-dependent mitophagy.

Monitoring autophagic flux in Caenorhabditis elegans using a p62/SQST-1 reporter.

Autophagy is a well-conserved self-degrading mechanism, which involves the elimination of unnecessary or damaged cellular constituents. Although extensively studied, many aspects regarding its tight regulation and its implication in health and disease remain elusive. The nematode Caenorhabditis elegans has been widely used as a simple multicellular model organism for studying the autophagic machinery per se, and uncover its multidimensional roles in the maintenance of cellular and organismal homeostasis.

The Synthetic Microneurotrophin BNN27 Affects Retinal Function in Rats With Streptozotocin-Induced Diabetes.

BNN27, a C17-spiroepoxy derivative of DHEA, was shown to have antiapoptotic properties via mechanisms involving the nerve growth factor receptors (tropomyosin-related kinase A [TrkA]/neurotrophin receptor p75 [p75]). In this study, we examined the effects of BNN27 on neural/glial cell function, apoptosis, and inflammation in the experimental rat streptozotocin (STZ) model of diabetic retinopathy (DR). The ability of BNN27 to activate the TrkA receptor and regulate p75 expression was investigated.