Co-chaperone BAG3 enters autophagic pathway via its interaction with microtubule associated protein 1 light chain 3 beta.

The co-chaperone BAG3 is a hub for a variety of cellular pathways via its multiple domains and its interaction with chaperones of the HSP70 family or small HSPs. During aging and under cellular stress conditions in particular, BAG3, together with molecular chaperones, ensures the sequestration of aggregated or aggregation-prone ubiquitinated proteins to the autophagic-lysosomal system via ubiquitin receptors. Accumulating evidence for BAG3-mediated selective autophagy independent of cargo ubiquitination led to analyses predicting a direct interaction of BAG3 with LC3 proteins.

Sirtuins and their influence on autophagy.

Sirtuins and autophagy are well-characterized agents that can promote longevity and protect individual organisms from age-associated diseases like neurodegenerative disorders. In recent years, more and more data has been obtained that discerned potential overlaps and crosstalk between Sirtuin proteins and autophagic activity. This review aims to summarize the advances within the field for each individual Sirtuin in mammalian systems.

Identification of an ERN1 target site within EGFP mRNA.

EGFP (enhanced green fluorescent protein) is one of the most common tools used in life sciences, including research focusing on proteostasis. Here we report that ERN1 (endoplasmic reticulum to nucleus signaling 1), which is upregulated by UPR (unfolded protein response), targets an RNA hairpin loop motif in EGFP mRNA. A silent mutation introduced into EGFP mRNA abolished the ERN1-dependent mRNA decay.

The selective degradation of sirtuins via macroautophagy in the MPP model of Parkinson's disease is promoted by conserved oxidation sites.

The sirtuin (SIRT) protein family has been of major research interest over the last decades because of their involvement in aging, cancer, and cell death. SIRTs have been implicated in gene and metabolic regulation through their capacity to remove acyl groups from lysine residues in proteins in an NAD-dependent manner, which may alter individual protein properties as well as the histone-DNA interaction. Since SIRTs regulate a wide range of different signaling cascades, a fine-tuned homeostasis of these proteins is imperative to guarantee the function and survival of the cell.

On the origin of BAG(3) and its consequences for an expansion of BAG3's role in protein homeostasis.

The B-cell CLL 2-associated athanogene (BAG) protein family in general and BAG3, in particular, are pivotal elements of cellular protein homeostasis, with BAG3 playing a major role in macroautophagy. In particular, in the contexts of senescence and degeneration, BAG3 has exhibited an essential role often related to its capabilities to organize and remove aggregated proteins. Exciting studies in different species ranging from human, murine, zebrafish, and plant samples have delivered vital insights into BAG3s' (and other BAG proteins') functions and their regulations.

Novel Insights into the Cellular Localization and Regulation of the Autophagosomal Proteins LC3A, LC3B and LC3C.

Macroautophagy is a conserved degradative process for maintaining cellular homeostasis and plays a key role in aging and various human disorders. The microtubule-associated protein 1A/1B light chain 3B (MAP1LC3B or LC3B) is commonly analyzed as a key marker for autophagosomes and as a proxy for autophagic flux. Three paralogues of the LC3 gene exist in humans: LC3A, LC3B and LC3C.

Retrotransposon activation by distressed mitochondria in neurons.

Retrotransposon activation occurs in a variety of neurological disorders including multiple sclerosis and Alzheimer's Disease. While the origins of disease-related retrotransposon activation have remained mostly unidentified, this phenomenon may well contribute to disease progression by inducing inflammation, disrupting transcription and, potentially, genomic insertion. Here, we report that the inhibition of mitochondrial respiratory chain complex I by pharmacological agents widely used to model Parkinson's disease leads to a significant increase in expression of the ORF1 protein of the long interspersed nucleotide element 1 (LINE1) retrotransposon in human dopaminergic LUHMES cells.

Author Correction: Metabolomics profiling reveals differential adaptation of major energy metabolism pathways associated with autophagy upon oxygen and glucose reduction.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

The role of Plasma Membrane Calcium ATPases (PMCAs) in neurodegenerative disorders.

Selective degeneration of differentiated neurons in the brain is the unifying feature of neurodegenerative disorders such as Parkinson's disease (PD) or Alzheimer's disease (AD). A broad spectrum of evidence indicates that initially subtle, but temporally early calcium dysregulation may be central to the selective neuronal vulnerability observed in these slowly progressing, chronic disorders. Moreover, it has long been evident that excitotoxicity and its major toxic effector mechanism, neuronal calcium overload, play a decisive role in the propagation of secondary neuronal death after acute brain injury from trauma or ischemia.

Metabolomics profiling reveals differential adaptation of major energy metabolism pathways associated with autophagy upon oxygen and glucose reduction.

The ability of cells to rearrange their metabolism plays an important role in compensating the energy shortage and may provide cell survival. Our study focuses on identifing the important adaptational changes under the conditions of oxygen and glucose reduction. Employing mass spectrometry-based metabolomics in combination with biochemistry and microscopy techniques we identified metabolites, proteins and biomolecular pathways alterations in primary human IMR90 fibroblasts upon energy deficits.