Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins.

Mitochondria are organelles with their own genomes, but they rely on the import of nuclear-encoded proteins that are translated by cytosolic ribosomes. Therefore, it is important to understand whether failures in the mitochondrial uptake of these nuclear-encoded proteins can cause proteotoxic stress and identify response mechanisms that may counteract it. Here, we report that upon impairments in mitochondrial protein import, high-risk precursor and immature forms of mitochondrial proteins form aberrant deposits in the cytosol.

Suppressing toxic aggregates: let MIA do it!

Mitochondrial activity is becoming an inherent aspect of cellular protein homeostasis (proteostasis). In this issue, Schlagowski et al (2021) report on the attractive notion that modulating mitochondrial protein import activity stimulates protein aggregate clearance in the cytosol, thereby affecting cytosolic proteostasis and its collapse observed in neurodegenerative diseases.

Mitochondrial control of cellular protein homeostasis.

Mitochondria are involved in several vital functions of the eukaryotic cell. The majority of mitochondrial proteins are coded by nuclear DNA. Constant import of proteins from the cytosol is a prerequisite for the efficient functioning of the organelle.

Structural Basis for the Inhibitory Effects of Ubistatins in the Ubiquitin-Proteasome Pathway.

The discovery of ubistatins, small molecules that impair proteasomal degradation of proteins by directly binding to polyubiquitin, makes ubiquitin itself a potential therapeutic target. Although ubistatins have the potential for drug development and clinical applications, the lack of structural details of ubiquitin-ubistatin interactions has impeded their development. Here, we characterized a panel of new ubistatin derivatives using functional and binding assays.

Structure of the Rpn13-Rpn2 complex provides insights for Rpn13 and Uch37 as anticancer targets.

Proteasome-ubiquitin receptor hRpn13/Adrm1 binds and activates deubiquitinating enzyme Uch37/UCHL5 and is targeted by bis-benzylidine piperidone RA190, which restricts cancer growth in mice xenografts. Here, we solve the structure of hRpn13 with a segment of hRpn2 that serves as its proteasome docking site; a proline-rich C-terminal hRpn2 extension stretches across a narrow canyon of the ubiquitin-binding hRpn13 Pru domain blocking an RA190-binding surface. Biophysical analyses in combination with cell-based assays indicate that hRpn13 binds preferentially to hRpn2 and proteasomes over RA190.

"The significance of cardiac magnetic resonance imaging in detection and monitoring of the treatment efficacy of heart involvement in eosinophilic granulomatosis with polyangiitis patients".

Background: Cardiac magnetic resonance imaging (CMRI) has emerged as a sensitive and non-invasive technique in the evaluation of cardiac lesions in eosinophilic granulomatosis with polyangiitis (EGPA) patients.

Objectives: To evaluate the ability of CMRI to detection and monitoring of the treatment efficacy in EGPA patients with cardiac involvement.

Methods: To the retrospective-prospective study were enrolled 33 cardiac involvement EGPA patients.

Myosin VI Contains a Compact Structural Motif that Binds to Ubiquitin Chains.

Myosin VI is critical for cargo trafficking and sorting during early endocytosis and autophagosome maturation, and abnormalities in these processes are linked to cancers, neurodegeneration, deafness, and hypertropic cardiomyopathy. We identify a structured domain in myosin VI, myosin VI ubiquitin-binding domain (MyUb), that binds to ubiquitin chains, especially those linked via K63, K11, and K29. Herein, we solve the solution structure of MyUb and MyUb:K63-linked diubiquitin.

Mycobacterium tuberculosis copper-regulated protein SocB is an intrinsically disordered protein that folds upon interaction with a synthetic phospholipid bilayer.

Multiple genes in Mycobacterium tuberculosis (Mtb) are regulated by copper including socAB (small orf induced by copper A and B), which is induced by copper and repressed by RicR (regulated in copper repressor). socA and socB encode hypothetical proteins of 61 and 54 amino acids, respectively. Here, we use biophysical and computational methods to evaluate the SocB structure.

DNA-damage-inducible 1 protein (Ddi1) contains an uncharacteristic ubiquitin-like domain that binds ubiquitin.

Ddi1 belongs to a family of shuttle proteins targeting polyubiquitinated substrates for proteasomal degradation. Unlike the other proteasomal shuttles, Rad23 and Dsk2, Ddi1 remains an enigma: its function is not fully understood and structural properties are poorly characterized. We determined the structure and binding properties of the ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains of Ddi1 from Saccharomyces cerevisiae.

[Disseminated pulmonary actinomycosis - an unusual presentation].

Actinomycosis is a rare, chronic infectious disease caused by anaerobic Gram-positive bacteria Actinomyces spp. They induces suppurative inflammation in tissues. They live as commensals in the oropharynx, interstitial tract and genital mucosa, causing almost exclusively endogenic infections.

[Severe hypoxemic respiratory insufficiency in a patient with hepato-pulmonary syndrome coexisting with interstitial lung disease of unknown etiology].

The coexistence of the interstitial lung disease and respiratory failure is rarely associated with extrapulmonary pathology. In patients with liver cirrhosis, hypoxemia may develop in the course of hepato-pulmonary syndrome (HPS), but radiological pathology seen in the course of HPS is of vascular origin, and thus typically not classified as interstitial lung disease. We present a patient with severe hypoxemic respiratory insufficiency in whom hepato-pulmonary syndrome coexisted with interstitial lung disease of unknown etiology.

[Allergic bronchopulmonary aspergillosis mimicking lung cancer in patients without bronchial asthma--case report].

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder characterized by hypersensitivity reaction to Aspergillus, mainly Aspergillus fumigatus with variable radiological findings. The prevalence of ABPA is about 1-2% in patients with asthma and 5-15% in patients with cystic fibrosis. Very infrequently the disease is diagnosed in patients without previous bronchial asthma.

Nonenzymatic assembly of natural polyubiquitin chains of any linkage composition and isotopic labeling scheme.

Polymeric chains made of a small protein ubiquitin act as molecular signals regulating a variety of cellular processes controlling essentially all aspects of eukaryotic biology. Uncovering the mechanisms that allow differently linked polyubiquitin chains to serve as distinct molecular signals requires the ability to make these chains with the native connectivity, defined length, linkage composition, and in sufficient quantities. This, however, has been a major impediment in the ubiquitin field.

[Disorders with elevated immunoglobulin E levels].

Immunoglobulin E (IgE) was first described in 1967. It has the lowest serum concentration of all circulating immunoglobulin isotypes. Serum IgE concentration at birth is low and rises until the age of 10-15 years.

Organising pneumonia and lung cancer - case report and review of the literature.

Organising pneumonia (OP) is a distinct clinicopathological entity resulting from pulmonary reaction to noxious environmental or endogenous factors, but also idiopathic cases have been noted. Frequently, small foci of OP accompany lung cancer infiltrations. Also OP is sometimes a reaction to radio- or chemotherapy, but it is rarely a predominant lesion in the course of lung cancer.

[Pneumatocele during long-lasting observation of hyper IgE patient].

Hyper IgE syndrome (Job's syndrome) is a rare multiorgan disease characterized by the triad: elevated serum IgE level, recurrent sinopulmonary infections, most often staphylococcal, and cutaneous cold abscesses starting in infancy. We report 21 years old patient with hyper IgE syndrome, diagnosed at age of 6 years on the basis of hyperimmunoglobulinaemia E and recurrent pulmonary and cutaneous infections. Now he was admitted because of pneumonia complicating with pneumatocele, which could not be resolved despite intravenous antibiotics.