Reviews

Mechanisms and therapeutic significance of autophagy modulation by antipsychotic drugs

Ljubica Vucicevic1, Maja Misirkic-Marjanovic1, Ljubica Harhaji-Trajkovic1, Nadja Maric2 and Vladimir Trajkovic3

INTRODUCTION The term autophagy (‘self-eating’ in Greek) refers to a group of evolutionarily conserved homeostatic mechanisms employed by eukaryotic cells to eliminate aged, unused, and damaged cytoplasmic components through lysosomal

Mitochondrial stress management: a dynamic journey

Miriam Valera-Alberni1,2 and Carles Canto1

Mitochondria undergo continuous challenges in the course of their life, from their generation to their degradation. These challenges include the management of reactive oxygen species, the proper assembly of mitochondrial respiratory complexes and the need to balance potential mutations in the mitochondrial DNA. The detection of damage and the ability to keep it under control is critical to fine-tune mitochondrial function to the organismal energy needs. In this review, we will analyze the multiple mechanisms that safeguard mitochondrial function in light of in crescendo damage. This sequence of events will include initial defense against excessive reactive oxygen species production, compensation mechanisms by the unfolded protein response (UPRmt), mitochondrial dynamics and elimination by mitophagy.

T lymphocytes against solid malignancies: winning ways to defeat tumours

Ignazio Caruana1,§, Luca Simula1,2,§, Franco Locatelli1,# and Silvia Campello2,3, #

INTRODUCTION When a tumour mass starts growing in the body, T lymphocytes are activated inside secondary lymphoid organs (SLOs) and mount an immune response against immuno-stimulating tumour antigens presented by

Mitochondrial dysfunction and its role in tissue-specific cellular stress

David Pacheu-Grau1, Robert Rucktäschel1 and Markus Deckers1

Mitochondrial bioenergetics require the coordination of two different and independent genomes. Mutations in either genome will affect mitochondrial functionality and produce different sources of cellular stress. Depending on the kind of defect and stress, different tissues and organs will be affected, leading to diverse pathological conditions. There is no curative therapy for mitochondrial diseases, nevertheless, there are strategies described that fight the various stress forms caused by the malfunctioning organelles. Here, we will revise the main kinds of stress generated by mutations in mitochondrial genes and outline several ways of fighting this stress.

Foie gras and liver regeneration: a fat dilemma

Maria Agnese Della Fazia1 and Giuseppe Servillo1

The liver has a unique ability of regenerating after injuries or partial loss of its mass. The mechanisms responsible for liver regeneration – mostly occurring when the hepatic tissue is damaged or functionally compromised by metabolic stress – have been studied in considerable detail over the last few decades, because this phenomenon has both basic-biology and clinical relevance. More specifically, recent interest has been focusing on the widespread occurrence of abnormal nutritional habits in the Western world that result in an increased prevalence of non-alcoholic fatty liver disease (NAFLD). NAFLD is closely associated with insulin resistance and dyslipidemia, and it represents a major clinical challenge. The disease may progress to steatohepatitis with persistent inflammation and progressive liver damage, both of which will compromise regeneration under conditions of partial hepatectomy in surgical oncology or in liver transplantation procedures. Here, we analyze the impact of ER stress and SIRT1 in lipid metabolism and in fatty liver pathology (...)

Epigenetic mechanisms behind cellular sensitivity to DNA damage

Amanda K. Williamson1, Zijing Zhu1 and Zhi-Min Yuan1

INTRODUCTION Epigenetics is the regulation of gene expression independent of the gene sequence itself via the interactions between DNA and proteins called histones [cite]10.4161/epi.24042[/cite]. In the nucleus, DNA is highly

Nucleolar Stress: hallmarks, sensing mechanism and diseases

Kai Yang1,2, Jie Yang1 and Jing Yi1

The nucleolus is a prominent subnuclear compartment, where ribosome biosynthesis takes place. Recently, the nucleolus has gained attention for its novel role in the regulation of cellular stress. Nucleolar stress is emerging as a new concept, which is characterized by diverse cellular insult-induced abnormalities in nucleolar structure and function, ultimately leading to activation of p53 or other stress signaling pathways and alterations in cell behavior. Despite a number of comprehensive reviews on this concept, straightforward and clear-cut way criteria for a nucleolar stress state, regarding the factors that elicit this state, the morphological and functional alterations as well as the rationale for p53 activation are still missing. Based on literature of the past two decades, we herein summarize the evolution of the concept and provide hallmarks of nucleolar stress. Along with updated information and thorough discussion of existing confusions in the field, we pay particular attention to the current understanding of the sensing mechanisms (...)

Putting together and taking apart: assembly and disassembly of the Rad51 nucleoprotein filament in DNA repair and genome stability

Tadas Andriuskevicius1, Oleksii Kotenko1 and Svetlana Makovets1

Homologous recombination is a key mechanism providing both genome stability and genetic diversity in all living organisms. Recombinases play a central role in this pathway: multiple protein subunits of Rad51 or its orthologues bind single-stranded DNA to form a nucleoprotein filament which is essential for initiating recombination events. Multiple factors are involved in the regulation of this step, both positively and negatively. In this review, we discuss Rad51 nucleoprotein assembly and disassembly, how it is regulated and what functional significance it has in genome maintenance.

How to use a multipurpose SNARE: The emerging role of Snap29 in cellular health

Valeria Mastrodonato1,#, Elena Morelli1,#  and Thomas Vaccari1

[table id=90 /] INTRODUCTION The specialized trafficking routes that evolved between compartments of the endomembrane system rely on a wide set of proteins, including primarily SNAREs, Rab GTPases and a

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