Anna Raffaello

Mitochondrial calcium uptake drives organelle remodeling to promote inflammasome-dependent cytokine release

Gaia Gherardi, Francesca Spinelli, Miriana Sbrissa, Martina Quagliata et autres

Abstract Mitochondrial Ca 2+ uptake shapes cellular signaling by modulating metabolism, cell death and cytosolic Ca 2+ dynamics, yet its pathological and therapeutic relevance remains undefined. Here, we show that Ca 2+ entry through the mitochondrial Ca 2+ uniporter (MCU) is required …

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YME1L-dependent regulation of mitochondrial Ca 2+ transport: a role for mitochondrial uptake protein 1 (MICU1) in nutrient sensing

Julian D. C. Serna, Donato D Angelo, Georgia Ohya, Rosario Rizzuto et autres

Abstract Mitochondrial calcium uptake via the mitochondrial calcium uniporter complex (MCUc) is tightly regulated by gatekeeper proteins such as MICU1 and MICU2. While long-term nutritional interventions have been shown to remodel the MCUc, its short-term regulation during postprandial transitions and acute nutrient …

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Impact of PARL-mediated mitochondrial protease activity on calcium regulation

Donato D'Angelo, A Saidi, Denis Vecellio Reane, Nicola Gasparini et autres

The presenilin-associated rhomboid-like protein (PARL) is a mitochondrial inner membrane serine protease that is a key regulator of several cellular processes, including apoptosis, metabolism, inflammation and stress responses. While recent studies suggest that PARL may play a role in mitochondrial calcium homeostasis, …

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Dependence of mitochondrial calcium signalling and dynamics on the disaggregase, CLPB

Donato D’Angelo, Víctor Hugo Sánchez-Vázquez, Benjamín Cartes-Saavedra, Denis Vecellio Reane et autres

Cells utilize protein disaggregases to avoid abnormal protein aggregation that causes many diseases. Among these, caseinolytic peptidase B protein homolog (CLPB) is localized in the mitochondrial intermembrane space and linked to human disease. Upon CLPB loss, MICU1 and MICU2, regulators of the …

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Creatine transporter (SLC6A8) knockout mice exhibit reduced muscle performance, disrupted mitochondrial Ca2+ homeostasis, and severe muscle atrophy

Irene Pertici, Donato D’Angelo, Denis Vecellio Reane, Massimo Reconditi et autres

Abstract Creatine (Cr) is essential for cellular energy homeostasis, particularly in muscle and brain tissues. Creatine Transporter Deficiency (CTD), an X-linked disorder caused by mutations in the SLC6A8 gene, disrupts Cr transport, leading to intellectual disability, speech delay, autism, epilepsy, and various …

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Mitochondrial calcium uptake orchestrates vertebrate pigmentation via transcriptional regulation of keratin filaments

Jyoti Tanwar, Kriti Ahuja, Akshay Sharma, Paras Sehgal et autres

Mitochondria regulate several physiological functions through mitochondrial Ca2+ dynamics. However, role of mitochondrial Ca2+ signaling in melanosome biology remains unknown. Here, we show that pigmentation requires mitochondrial Ca2+ uptake. In vitro gain and loss of function studies demonstrate that mitochondrial Ca2+ uniporter …

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Mitochondria can substitute for parvalbumin to lower cytosolic calcium levels in the murine fast skeletal muscle

Lorenzo Marcucci, Leonardo Nogara, Marta Canato, Elena Angela Pia Germinario et autres

Abstract Aim Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal muscle fibers. Previous work showed that PV ablation has a limited impact on cytosolic Ca2+ ([Ca2+]cyto) transients and contractile response, while it enhances mitochondrial density and mitochondrial matrix‐free calcium …

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Reiterated male-to-female violence disrupts hippocampal estrogen receptor β expression, prompting anxiety-like behavior

Jacopo Agrimi, Lucia Bernardele, Naeem Sbaiti, Marco Brondi et autres

Intimate partner violence (IPV) is a significant public health concern whose neurological/behavioral sequelae remain to be mechanistically explained. Using a mouse model recapitulating an IPV scenario, we evaluated the female brain neuroendocrine alterations produced by a reiterated male-to-female violent interaction (RMFVI). RMFVI …

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Unravelling the complexity of the mitochondrial Ca2+ uniporter: regulation, tissue specificity, and physiological implications

Denis Vecellio Reane, Julian D. C. Serna, Anna Raffaello

Calcium (Ca2+) signalling acts a pleiotropic message within the cell that is decoded by the mitochondria through a sophisticated ion channel known as the Mitochondrial Ca2+ Uniporter (MCU) complex. Under physiological conditions, mitochondrial Ca2+ signalling is crucial for coordinating cell activation with …

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Neither too much nor too little: mitochondrial calcium concentration as a balance between physiological and pathological conditions

Donato D’Angelo, Denis Vecellio Reane, Anna Raffaello

Ca 2+ ions serve as pleiotropic second messengers in the cell, regulating several cellular processes. Mitochondria play a fundamental role in Ca 2+ homeostasis since mitochondrial Ca 2+ (mitCa 2+ ) is a key regulator of oxidative metabolism and cell death. MitCa …

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Mitochondrial Ca2+ and functional adaptations to nutritional signals: insights from caloric restriction

Julian D. C. Serna, Alicia Juliana Kowaltowski, Camille C. Caldeira da Silva, Andressa Rodrigues Amaral et autres

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The mitochondrial calcium uniporter complex–A play in five acts

Agnese De Mario, Donato D'Angelo, Giuseppe Zanotti, Anna Raffaello et autres

Mitochondrial Ca2+ (mitCa2+) uptake controls both intraorganellar and cytosolic functions. Within the organelle, [Ca2+] increases regulate the activity of tricarboxylic acid (TCA) cycle enzymes, thus sustaining oxidative metabolism and ATP production. Reactive oxygen species (ROS) are also generated as side products of …

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