Volume 4 (2020)

Fine intercellular connections in development: TNTs, cytonemes, or intercellular bridges?

Olga Korenkova1,2, Anna Pepe1 and Chiara Zurzolo1

Intercellular communication is a fundamental property of multicellular organisms, necessary for their adequate responses to changing environment. Tunneling nanotubes (TNTs) represent a novel means of intercellular communication being a long cell-to-cell conduit. TNTs are actively formed under a broad range of stresses and are also proposed to exist under physiological conditions. Development is a physiological condition of particular interest, as it requires fine coordination. Here we discuss whether protrusions shown to exist during embryonic development of different species could be TNTs or if they represent other types of cell structure, like cytonemes or intercellular bridges, that are suggested to play an important role in development.

Kynurenine: an oncometabolite in colon cancer

Niranjan Venkateswaran1 and Maralice Conacci-Sorrell1,2,3

TRYPTOPHAN IS PREFERENTIALLY CONVERTED INTO KYNURENINE IN COLON CANCER Tryptophan can be utilized in three ways intracellularly: it can be incorporated into newly synthesized proteins, it can be processed by

Necroptosis, tumor necrosis and tumorigenesis

Zheng-gang Liu1 and Delong Jiao1

INTRODUCTION Cell death can happen through either an active, regulated process, known as programmed cell death, or a passive, uncontrolled course. Because of the dramatic morphological differences of these two

Fatty acids – from energy substrates to key regulators of cell survival, proliferation and effector function

Danilo Cucchi1, Dolores Camacho-Muñoz2, Michelangelo Certo3, Valentina Pucino3, Anna Nicolaou2,4 and Claudio Mauro3,5,6

Recent advances in immunology and cancer research show that fatty acids, their metabolism and their sensing have a crucial role in the biology of many different cell types. Indeed, they are able to affect cellular behaviour with great implications for pathophysiology. Both the catabolic and anabolic pathways of fatty acids present us with a number of enzymes, receptors and agonists/antagonists that are potential therapeutic targets, some of which have already been successfully pursued. Fatty acids can affect the differentiation of immune cells, particularly T cells, as well as their activation and function, with important consequences for the balance between anti- and pro-inflammatory signals in immune diseases, such as rheumatoid arthritis, psoriasis, diabetes, obesity and cardiovascular conditions. In the context of cancer biology, fatty acids mainly provide substrates for (…)

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High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer’s disease

Maria Calvo-Rodriguez1 and Brian J. Bacskai1

MITOCHONDRIAL CALCIUM OVERLOAD AFTER PLAQUE DEPOSITION Ca2+ is essential for the normal function of mitochondrial activity, and therefore Ca2+ levels are tightly regulated in mitochondria. However, excessive levels of Ca2+

The role of lipids in autophagy and its implication in neurodegeneration

Sergio Hernandez-Diaz1,2 and Sandra-Fausia Soukup1,2

Neurodegenerative diseases are, at present, major socio-economic burdens without effective treatments and their increasing prevalence means that these diseases will be a challenge for future generations. Neurodegenerative diseases may differ in etiology and pathology but are often caused by the accumulation of dysfunctional and aggregation-prone proteins. Autophagy, a conserved cellular mechanism, deals with cellular stress and waste product build-up and has been shown to reduce the accumulation of dysfunctional proteins in animal models of neurodegenerative diseases. Historically, progress in understanding the precise function of lipids has traditionally been far behind other biological molecules (like proteins) but emerging works demonstrate the importance of lipids in the autophagy pathway and how the disturbance of lipid metabolism is connected to neurodegeneration. Here we review how altered autophagy and the disturbance of lipid metabolism, particularly of phosphoinositols and sphingolipids, feature in neurodegenerative diseases and address work from the field that suggests that these potentially offer an opportunity of therapeutic intervention.

Immune system activation by natural products and complex fractions: a network pharmacology approach in cancer treatment

Alejandra Gomez-Cadena1,2,3, Alfonso Barreto3, Susana Fiorentino3 and Camilla Jandus1,2

INTRODUCTION Over the past decade, immunotherapy has become a promising approach to treat cancer and is now being combined with standard chemotherapy and immune response activators to improve the outcome

Mitochondria, mitophagy, and metabolic disease: towards assembling the puzzle

Zhiyong Chen1, Marine Berquez1 and Alessandro Luciani1

Mitochondria — the intracellular powerhouse that stores energy and signaling metabolites — are highly dynamic, double-membrane organelles that enact metabolism, hence sustaining physiology and organismal health. The maintenance of these

Mitochondria in cancer

Debora Grasso1, Luca X. Zampieri1, Tânia Capelôa1, Justine A. Van de Velde1 and Pierre Sonveaux1

The rediscovery and reinterpretation of the Warburg effect in the year 2000 occulted for almost a decade the key functions exerted by mitochondria in cancer cells. Until recent times, the scientific community indeed focused on constitutive glycolysis as a hallmark of cancer cells, which it is not, largely ignoring the contribution of mitochondria to the malignancy of oxidative and glycolytic cancer cells, being Warburgian or merely adapted to hypoxia. In this review, we highlight that mitochondria are not only powerhouses in some cancer cells, but also dynamic regulators of life, death, proliferation, motion and stemness in other types of cancer cells. Similar to the cells that host them, mitochondria are capable to adapt to tumoral conditions, and probably to evolve to ‘oncogenic mitochondria’ capable of transferring malignant capacities to recipient cells. In the wider quest of metabolic modulators of cancer, treatments have already been identified targeting mitochondria in cancer cells, but the field is still in infancy.

HIF1α or mitophagy: which drives cardiomyocyte differentiation?

Beatriz Villarejo-Zori1,#, Juan Ignacio Jiménez-Loygorri1,# and Patricia Boya1

Cardiomyocytes (CMs) are the main cellular component of the heart's atria and ventricles, and their contractile capacity is the engine that drives blood flow throughout the body. The differentiation of

High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer’s disease

Maria Calvo-Rodriguez1 and Brian J. Bacskai1

MITOCHONDRIAL CALCIUM OVERLOAD AFTER PLAQUE DEPOSITION Ca2+ is essential for the normal function of mitochondrial activity, and therefore Ca2+ levels are tightly regulated in mitochondria. However, excessive levels of Ca2+

The role of lipids in autophagy and its implication in neurodegeneration

Sergio Hernandez-Diaz1,2 and Sandra-Fausia Soukup1,2

Neurodegenerative diseases are, at present, major socio-economic burdens without effective treatments and their increasing prevalence means that these diseases will be a challenge for future generations. Neurodegenerative diseases may differ in etiology and pathology but are often caused by the accumulation of dysfunctional and aggregation-prone proteins. Autophagy, a conserved cellular mechanism, deals with cellular stress and waste product build-up and has been shown to reduce the accumulation of dysfunctional proteins in animal models of neurodegenerative diseases. Historically, progress in understanding the precise function of lipids has traditionally been far behind other biological molecules (like proteins) but emerging works demonstrate the importance of lipids in the autophagy pathway and how the disturbance of lipid metabolism is connected to neurodegeneration. Here we review how altered autophagy and the disturbance of lipid metabolism, particularly of phosphoinositols and sphingolipids, feature in neurodegenerative diseases and address work from the field that suggests that these potentially offer an opportunity of therapeutic intervention.

Immune system activation by natural products and complex fractions: a network pharmacology approach in cancer treatment

Alejandra Gomez-Cadena1,2,3, Alfonso Barreto3, Susana Fiorentino3 and Camilla Jandus1,2

INTRODUCTION Over the past decade, immunotherapy has become a promising approach to treat cancer and is now being combined with standard chemotherapy and immune response activators to improve the outcome

Mitochondria, mitophagy, and metabolic disease: towards assembling the puzzle

Zhiyong Chen1, Marine Berquez1 and Alessandro Luciani1

Mitochondria — the intracellular powerhouse that stores energy and signaling metabolites — are highly dynamic, double-membrane organelles that enact metabolism, hence sustaining physiology and organismal health. The maintenance of these

Mitochondria in cancer

Debora Grasso1, Luca X. Zampieri1, Tânia Capelôa1, Justine A. Van de Velde1 and Pierre Sonveaux1

The rediscovery and reinterpretation of the Warburg effect in the year 2000 occulted for almost a decade the key functions exerted by mitochondria in cancer cells. Until recent times, the scientific community indeed focused on constitutive glycolysis as a hallmark of cancer cells, which it is not, largely ignoring the contribution of mitochondria to the malignancy of oxidative and glycolytic cancer cells, being Warburgian or merely adapted to hypoxia. In this review, we highlight that mitochondria are not only powerhouses in some cancer cells, but also dynamic regulators of life, death, proliferation, motion and stemness in other types of cancer cells. Similar to the cells that host them, mitochondria are capable to adapt to tumoral conditions, and probably to evolve to ‘oncogenic mitochondria’ capable of transferring malignant capacities to recipient cells. In the wider quest of metabolic modulators of cancer, treatments have already been identified targeting mitochondria in cancer cells, but the field is still in infancy.

Towards understanding the role of Receptor Expression Enhancing Protein 5 (REEP5) in cardiac muscle and beyond

Shin-Haw Lee1,2, Sina Hadipour-Lakmehsari1,2 and Anthony O. Gramolini1,2

DISCOVERY OF REEP5 Cardiac membrane proteins play an important role in regulating normal beat-to-beat function of the heart given their importance in coordinating spontaneous contractions of cardiomyocytes in the heart.

Role of RNA Binding Proteins with prion-like domains in muscle and neuromuscular diseases

Gina Picchiarelli1 and Luc Dupuis1

A number of neuromuscular and muscular diseases, including amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and several myopathies, are associated to mutations in related RNA-binding proteins (RBPs), including TDP-43, FUS, MATR3 or hnRNPA1/B2. These proteins harbor similar modular primary sequence with RNA binding motifs and low complexity domains, that enables them to phase separate and create liquid microdomains. These RBPs have been shown to critically regulate multiple events of RNA lifecycle, including transcriptional events, splicing and RNA trafficking and sequestration. Here, we review the roles of these disease-related RBPs in muscle and motor neurons, and how their dysfunction in these cell types might contribute to disease.

Biomechanical stress regulates mammalian tooth replacement

Xiaoshan Wu1,2 and Songlin Wang1,3

The DT eruption released a biomechanical stress of about 3-20 kPa inside the mandible. By culturing the mandible slice in vitro, the SDL of the PT immediately transitioned into the

Biomechanical stress provides a second hit in the establishment of BMP/TGFβ-related vascular disorders

Christian Hiepen1, Jerome Jatzlau1 and Petra Knaus1

BMPR2 MUTATIONS PRIME FOR PAH BUT REQUIRE A SECOND HIT While BMPR2 mutations appear as one of the main genetic drivers for HPAH, low BMPR2 expression is also found in

A sympathetic gut connection drives the metabolic benefits of Roux-en-Y gastric bypass

Mohammed K. Hankir1

Surgery is regarded by many as the go-to treatment option for severe obesity; yet how physically altering the gastrointestinal tract produces such striking results on body weight and overall metabolic health is poorly understood. In a recent issue of Cell Reports Ye et al. (2020) compare mouse models of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the two most commonly performed weight loss surgeries in the clinic today, to show that the former reconfiguring procedure selectively increases resting metabolic rate through splanchnic nerve-mediated browning of mesenteric white fat. More significantly, they demonstrate that this effect for RYGB is required for the maintained negative energy balance and improved glycemic control that it confers.

Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma

James J. Hsieh1 and Emily H. Cheng2,3,4

INTRODUCTION On average a human adult body encompasses fifty trillion cells (~5×1013) with a daily turnover of hundred billion cells (~1011) within which each contains two copies of ~three billion

HIF1α or mitophagy: which drives cardiomyocyte differentiation?

Beatriz Villarejo-Zori1,#, Juan Ignacio Jiménez-Loygorri1,# and Patricia Boya1

Cardiomyocytes (CMs) are the main cellular component of the heart's atria and ventricles, and their contractile capacity is the engine that drives blood flow throughout the body. The differentiation of

Copper – a novel stimulator of autophagy

Hans Zischka1,2 and Guido Kroemer3-7

In biomedicine, the transition metal copper has a Janus-faced dual role, as an essential but static cofactor of vital enzymes but also as a highly detrimental poison, if in excess.

Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses

Didier Raoult1, Alimuddin Zumla2,3, Franco Locatelli4, Giuseppe Ippolito5 and Guido Kroemer6-10,*

INTRODUCTION Infections have been limiting quality of life and longevity throughout human history. Endemic infections have been associated to a significant number of avoidable deaths and a significant increase of

ACBP is an appetite stimulator across phylogenetic barriers

Frank Madeo1,2, Nektarios Tavernarakis3,4, José M. Bravo-San Pedro5-7,# and Guido Kroemer5-10,#

Human civilization is unique with respect to the organization of our natural environment, allowing constant supply of nutrients to most individuals in developed countries, contrasting with the natural fluctuation in

Necroptosis, tumor necrosis and tumorigenesis

Zheng-gang Liu1 and Delong Jiao1

INTRODUCTION Cell death can happen through either an active, regulated process, known as programmed cell death, or a passive, uncontrolled course. Because of the dramatic morphological differences of these two