Mateus Milani

The lysosomal channel RECS1 regulates extracellular vesicle biogenesis

Mateus Milani, Nicolás Montes-Bravo, Claudia Sepúlveda-Quiñenao, Jordan Burton et autres

ABSTRACT Lysosomal ion channels play key roles in regulating membrane trafficking, autophagy, and cell death. RECS1 is a pH-sensitive lysosomal calcium channel previously implicated in lysosome-mediated apoptosis. Here, we identify a novel role for RECS1 in exosome biology. Using immunoprecipitation followed by …

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Targeting the ER stress sensor IRE1 protects the liver from fibrosis through the downregulation of the proteostasis factor P4HB/PDIA1

Younis Hazari, Lama Habbouche, Valeria A. Garcia Lopez, Hery Urra et autres

BACKGROUND AIMS: Collagen is the main cargo of the secretory pathway, contributing to hepatic fibrogenesis due to extensive accumulation of extracellular matrix. An excess of collagen deposition is a characteristic feature of several chronic liver diseases. Collagen overproduction imposes pressure on the …

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Author Reply to Peer Reviews of Targeting the ER stress sensor IRE1 protects the liver from fibrosis through the downregulation of the proteostasis factor P4HB/PDIA1

Younis Hazari, Hery Urra, Valeria A. Garcia Lopez, Lama Habbouche et autres

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BAX and BAK expression triggers multiple IRE1 signaling outputs under ER stress

Claudia Sepúlveda, Mateus Milani, Vania Morales, Giovanni Tamburinni et autres

Abstract Adaptation to endoplasmic reticulum (ER) stress depends on the activation of the unfolded protein response (UPR) stress sensor inositol-requiring enzyme 1 alpha (IRE1). IRE1 is a central ER stress sensors, that signals through the activation of its RNase domain to catalyze …

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Calcium signaling in lysosome-dependent cell death

Mateus Milani, Philippe Pihán, Claudio A. Hetz

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The endoplasmic reticulum stress sensor IRE1 regulates collagen secretion through the enforcement of the proteostasis factor P4HB/PDIA1 contributing to liver damage and fibrosis

Younis Hazari, Hery Urra, Valeria A. Garcia Lopez, Javier Diaz et autres

Abstract Collagen is one the most abundant proteins and the main cargo of the secretory pathway, contributing to hepatic fibrosis and cirrhosis due to excessive deposition of extracellular matrix. Here we investigated the possible contribution of the unfolded protein response, the main …

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Proteomic Analysis of Huntington’s Disease Medium Spiny Neurons Identifies Alterations in Lipid Droplets

Kizito‐Tshitoko Tshilenge, Carlos Galicia Aguirre, Joanna Bons, Akos A. Gerencser et autres

Huntington's disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin (HTT) gene. The resulting polyglutamine (polyQ) tract alters the function of the HTT protein. Although HTT is expressed in different tissues, the medium-spiny projection neurons (MSNs) …

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Mitochondria-associated niches in health and disease

Mateus Milani, Philippe Pihán

The appreciation of the importance of interorganelle contacts has steadily increased over the past decades. Advances in imaging, molecular biology and bioinformatic techniques allowed the discovery of new mechanisms involved in the interaction and communication between organelles, providing novel insights into the …

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Novel roles of RTN4 and CLIMP-63 in regulating mitochondrial structure, bioenergetics and apoptosis

Rachel Carter, Mateus Milani, Alison J. Beckett, Shiyu Liu et autres

The recruitment of DRP1 to mitochondrial membranes prior to fission is facilitated by the wrapping of endoplasmic reticulum (ER) membranes around the mitochondria. To investigate the complex interplay between the ER membranes and DRP1 in the context of mitochondrial structure and function, …

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Proapoptotic RECS1: a requisite gateway to lysosomal dysfunction and death

Claudio A. Hetz, Philippe Pihán, Mateus Milani

For a long time since their discovery by Christian de Duve in the 1950s, lysosomes have been referred to almost exclusively as passive garbage bags; the endpoint in the degradation of intra- and extracellular cargo. The catabolic function of lysosomes is accomplished …

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Exploring the potential of BH3 mimetic therapy in squamous cell carcinoma of the head and neck

Rachel Carter, Mateus Milani, Michael Bruce Butterworth, Ahoud Alotibi et autres

Abstract Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer worldwide, with overall survival of less than 50%. Current therapeutic strategies involving a combination of surgery, radiation, and/or chemotherapy are associated with debilitating side effects, highlighting …

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DRP-1 functions independently of mitochondrial structural perturbations to facilitate BH3 mimetic-mediated apoptosis

Mateus Milani, Alison J. Beckett, Aoula Al-Zebeeby, Xu Luo et autres

Abstract Maintenance of mitochondrial integrity is critical for normal cellular homoeostasis. Most cells respond to stress stimuli and undergo apoptosis by perturbing mitochondrial structure and function to release proteins, such as cytochrome c, which are essential for the execution of the intrinsic …

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