Reviews

Immunometabolic cross-talk in the inflamed heart

Federica M. Marelli-Berg1,3 and Dunja Aksentijevic2,3

Inflammatory processes underlie many diseases associated with injury of the heart muscle, including conditions without an obvious inflammatory pathogenic component such as hypertensive and diabetic cardiomyopathy. Persistence of cardiac inflammation can cause irreversible structural and functional deficits. Some are induced by direct damage of the heart muscle by cellular and soluble mediators but also by metabolic adaptations sustained by the inflammatory microenvironment. It is well established that both cardiomyocytes and immune cells undergo metabolic reprogramming in the site of inflammation, which allow them to deal with decreased availability of nutrients and oxygen. However, like in cancer, competition for nutrients and increased production of signalling metabolites such as lactate initiate a metabolic cross-talk between immune cells and cardiomyocytes which, we propose, might tip the balance between resolution of the inflammation versus adverse cardiac remodeling. Here we review our current understanding of the metabolic reprogramming of both heart tissue and immune (...)

The role of epigenetics in hypothalamic energy balance control: implications for obesity

Arnaud Obri1 and Marc Claret1,2

INTRODUCTION The prevalence of obesity continues to increase worldwide. This trend is of concern because of its dramatic economic impact, concomitant decreased lifespan and increased comorbidities, such as hypertension, cardiovascular

Stress and catecholamines modulate the bone marrow microenvironment to promote tumorigenesis

Pauline Hanns1, Anna M. Paczulla1, Michael Medinger2, Martina Konantz1 and Claudia Lengerke1,2

High vascularization and locally secreted factors make the bone marrow (BM) microenvironment particularly hospitable for tumor cells and bones to a preferred metastatic site for disseminated cancer cells of different origins. Cancer cell homing and proliferation in the BM are amongst other regulated by complex interactions with BM niche cells (e.g. osteoblasts, endothelial cells and mesenchymal stromal cells (MSCs)), resident hematopoietic stem and progenitor cells (HSPCs) and pro-angiogenic cytokines leading to enhanced BM microvessel densities during malignant progression. Stress and catecholamine neurotransmitters released in response to activation of the sympathetic nervous system (SNS) reportedly modulate various BM cells and may thereby influence cancer progression. Here we review the role of catecholamines during tumorigenesis with particular focus on pro-tumorigenic effects mediated by the BM niche.

Remodeling of mitochondrial morphology and function: an emerging hallmark of cellular reprogramming

Anuj Rastogi1, Piyush Joshi2,3, Ela Contreras1 and Vivian Gama1,2,3,4

Research in the stem cell field has traditionally focused on understanding key transcriptional factors that provide pluripotent cell identity. However, much less is known about other critical non-transcriptional signaling networks that govern stem cell identity. Although we continue to gain critical insights into the mechanisms underlying mitochondrial morphology and function during cellular reprogramming – the process of reverting the fate of a differentiated cell into a stem cell, many uncertainties remain. Recent studies suggest an emerging landscape in which mitochondrial morphology and function have an active role in maintaining and regulating changes in cell identity. In this review, we will focus on these emerging concepts as crucial modulators of cellular reprogramming. Recognition of the widespread applicability of these concepts will increase our understanding of the mitochondrial mechanisms involved in cell identity, cell fate and disease.

The sensing of mitochondrial DAMPs by non-immune cells

Aida Rodríguez-Nuevo1,2,3 and Antonio Zorzano1,2,3

MITOCHONDRIA ARE IMMUNOGENIC ORGANELLES The efficiency of the innate immune system is determined by the capacity of distinct cell types to discriminate self from non-self structures. The dysregulation of this

Biology and clinical relevance of EpCAM

Laura Keller1,§, Stefan Werner1,§ and Klaus Pantel1

INTRODUCTION The EpCAM protein was discovered almost 40 years ago as a major epithelial carcinoma antigen by M. Herlyn and colleagues, as a result of its property to generate monoclonal

Recent progress in the role of autophagy in neurological diseases

Tian Meng1,#, Shiyin Lin1,#, Haixia Zhuang1, Haofeng Huang2, Zhengjie He1, Yongquan Hu1, Qing Gong3 and Du Feng1

Autophagy (here refers to macroautophagy) is a catabolic pathway by which large protein aggregates and damaged organelles are first sequestered into a double-membraned structure called autophagosome and then delivered to lysosome for destruction. Recently, tremendous progress has been made to elucidate the molecular mechanism and functions of this essential cellular metabolic process. In addition to being either a rubbish clearing system or a cellular surviving program in response to different stresses, autophagy plays important roles in a large number of pathophysiological conditions, such as cancer, diabetes, and especially neurodegenerative disorders. Here we review recent progress in the role of autophagy in neurological diseases and discuss how dysregulation of autophagy initiation, autophagosome formation, maturation, and/or autophagosome-lysosomal fusion step contributes to the pathogenesis of these disorders in the nervous system.

Constitutional Mosaic Epimutations – a hidden cause of cancer?

Per E. Lønning1,2, Hans P. Eikesdal1,2, Inger M. Løes1,2 and Stian Knappskog1,2

Silencing of tumor suppressor genes by promoter hypermethylation is a key mechanism to facilitate cancer progression in many malignancies. While promoter hypermethylation can occur at later stages of the carcinogenesis process, constitutional methylation of key tumor suppressors may be an initiating event whereby cancer is started. Constitutional BRCA1 methylation due to cis-acting germline genetic variants is associated with a high risk of breast and ovarian cancer. However, this seems to be a rare event, restricted to a very limited number of families. In contrast, mosaic constitutional BRCA1 methylation is detected in 4-7% of newborn females without germline BRCA1 mutations. While the cause of such methylation is poorly understood, mosaic normal tissue BRCA1 methylation is associated with a 2-3 fold increased risk of high-grade serous ovarian cancer (HGSOC). As such, BRCA1 methylation may be the cause of a significant number of ovarian cancers. Given the molecular similarities between HGSOC and basal-like breast cancer, the (...)

Role of protein phosphatases PP1, PP2A, PP4 and Cdc14 in the DNA damage response

Facundo Ramos1, María Teresa Villoria1, Esmeralda Alonso-Rodríguez1 and Andrés Clemente-Blanco1

INTRODUCTION Cells are constantly suffering endogenous and exogenous stresses that affect the integrity of the genetic material. It has been estimated that every cell of our body is exposed to

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