1. Mitochondria can substitute for parvalbumin to lowercytosolic calcium levels in the murine fast skeletal muscleLorenzo Marcucci, Leonardo Nogara, Marta Canato, Elena Germinario, Anna Raffaello, Michela Carraro, Paolo Bernardi, Laura Pietrangelo, Simona Boncompagni, Feliciano Protasi, Nazareno Paolocci, Carlo Reggiani, 2024, izvirni znanstveni članek Povzetek: Aim: Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal musclefibers. Previous work showed that PV ablation has a limited impact on cytosolicCa2+ ([Ca2+]cyto) transients and contractile response, while it enhances mitochon-drial density and mitochondrial matrix-free calcium concentration ([Ca2+]mito).Here, we aimed to quantitatively test the hypothesis that mitochondria act tocompensate for PV deficiency.Methods: We determined the free Ca 2+ redistribution during a 2 s 60 Hz tetanicstimulation in the sarcoplasmic reticulum, cytosol, and mitochondria. Via a re-action–diffusion Ca 2+ model, we quantitatively evaluated mitochondrial uptakeand storage capacity requirements to compensate for PV lack and analyzed pos-sible extracellular export.Results: [Ca 2+]mito during tetanic stimulation is greater in knock-out (KO)(1362 ± 392 nM) than in wild-type (WT) (855 ± 392 nM), p < 0.05. Under the as-sumption of a non-linear intramitochondrial buffering, the model predicts an ac-cumulation of 725 μmoles/Lfiber (buffering ratio 1:11 000) in KO, much higherthan in WT (137 μmoles/Lfiber, ratio 1:4500). The required transport rate via mi-tochondrial calcium uniporter (MCU) reaches 3 mM/s, compatible with availableliterature. TEM images of calcium entry units and Mn2+ quenching showed a greater capacity of store- operated calcium entry in KO compared to WT. However,levels of [Ca 2+]cyto during tetanic stimulation were not modulated to variations ofextracellular calcium.Conclusions: The model-based analysis of experimentally determined calciumdistribution during tetanic stimulation showed that mitochondria can act as abuffer to compensate for the lack of PV. This result contributes to a better under-standing of mitochondria's role in modulating [Ca2+]cyto in skeletal muscle fibers.
Ključne besede: calcium, mitochondria, mouse skeletal muscle fibers, parvalbumin, reaction-diffusion model
Objavljeno v DiRROS: 13.11.2024; Ogledov: 107; Prenosov: 67
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2. Organelles and phytohormones : a network of interactions in plant stress responsesAndras Bittner, Agata Cieśla, Kristina Gruden, Tjaša Lukan, Sakil Mahmud, Markus Teige, Ute Vothknecht, Bernhard Wurzinger, 2022, pregledni znanstveni članek Povzetek: Phytohormones are major signaling components that contribute to nearly all aspects of plant life. They constitute an interconnected communication network to fine-tune growth and development in response to the ever-changing environment. To this end, they have to coordinate with other signaling components, such as reactive oxygen species and calcium signals. On the one hand, the two endosymbiotic organelles, plastids and mitochondria, control various aspects of phytohormone signaling and harbor important steps of hormone precursor biosynthesis. On the other hand, phytohormones have feedback actions on organellar functions. In addition, organelles and phytohormones often act in parallel in a coordinated matter to regulate cellular functions. Therefore, linking organelle functions with increasing knowledge of phytohormone biosynthesis, perception, and signaling will reveal new aspects of plant stress tolerance. In this review, we highlight recent work on organelle–phytohormone interactions focusing on the major stress-related hormones abscisic acid, jasmonates, salicylic acid, and ethylene.
Ključne besede: abscisic acid (ABA), chloroplast, ethylene, mitochondria, jasmonates, plant organelles, phytohormones, salicylic acid (SA), plastids, stress signaling, retrograde signaling
Objavljeno v DiRROS: 05.08.2024; Ogledov: 275; Prenosov: 223
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3. Increased mitochondrial activity in a novel IDH1-R132H mutant human oligodendroglioma xenograft model : in situ detection of 2-HG and [alpha]-KGAnna C. Navis, Simone P. Niclou, Fred Fack, Daniel Stieber, Sanne A. M. van Lith, Kiek Verrijp, Alan F. Wright, Jonathan Stauber, Bastiaan Tops, Irene Otte-Holler, Ron A. Wevers, Arno van Rooij, Stefan Pusch, Andreas von Deimling, Wikky Tigchelaar, Cornelis J. F. van Noorden, Pieter Wesseling, William P. J. Leenders, 2013, izvirni znanstveni članek Povzetek: Background
Point mutations in genes encoding NADP+-dependent isocitrate dehydrogenases (especially IDH1) are common in lower grade diffuse gliomas and secondary glioblastomas and occur early during tumor development. The contribution of these mutations to gliomagenesis is not completely understood and research is hampered by the lack of relevant tumor models. We previously described the development of the patient-derived high-grade oligodendroglioma xenograft model E478 that carries the commonly occurring IDH1-R132H mutation. We here report on the analyses of E478 xenografts at the genetic, histologic and metabolic level.
Results
LC-MS and in situ mass spectrometric imaging by LESA-nano ESI-FTICR revealed high levels of the proposed oncometabolite D-2-hydroxyglutarate (D-2HG), the product of enzymatic conversion of α-ketoglutarate (α-KG) by IDH1-R132H, in the tumor but not in surrounding brain parenchyma. α-KG levels and total NADP+-dependent IDH activity were similar in IDH1-mutant and -wildtype xenografts, demonstrating that IDH1-mutated cancer cells maintain α-KG levels. Interestingly, IDH1-mutant tumor cells in vivo present with high densities of mitochondria and increased levels of mitochondrial activity as compared to IDH1-wildtype xenografts. It is not yet clear whether this altered mitochondrial activity is a driver or a consequence of tumorigenesis.
Conclusions
The oligodendroglioma model presented here is a valuable model for further functional elucidation of the effects of IDH1 mutations on tumor metabolism and may aid in the rational development of novel therapeutic strategies for the large subgroup of gliomas carrying IDH1 mutations.
Ključne besede: gliomaI, IDH mutations, xenograft, D-2-hydroxyglutarate, [alpha]-ketoglutarate, mitochondria: LESA-nano ESI-FTIC
Objavljeno v DiRROS: 02.08.2024; Ogledov: 312; Prenosov: 240
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4. MitomiRs: their roles in mitochondria and importance in cancer cell metabolismAndrej Renčelj, Nada Gvozdenović, Maja Čemažar, 2021, pregledni znanstveni članek Povzetek: Background. MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in almost all biological path- ways. They regulate post-transcriptional gene expression by binding to the 3%untranslated region (3%UTR) of messenger RNAs (mRNAs). MitomiRs are miRNAs of nuclear or mitochondrial origin that are localized in mitochondria and have a crucial role in regulation of mitochondrial function and metabolism. In eukaryotes, mitochondria are the major sites of oxidative metabolism of sugars, lipids, amino acids, and other bio-macromolecules. They are also the main sites of adenosine triphosphate (ATP) production. Conclusions. In the review, we discuss the role of mitomiRs in mitochondria and introduce currently well studied mito- miRs, their target genes and functions. We also discuss their role in cancer initiation and progression through the regu- lation of mRNA expression in mitochondria. MitomiRs directly target key molecules such as transporters or enzymes in cell metabolism and regulate several oncogenic signaling pathways. They also play an important role in the Warburg effect, which is vital for cancer cells to maintain their proliferative potential. In addition, we discuss how they indirectly upregulate hexokinase 2 (HK2), an enzyme involved in glucose phosphorylation, and thus may affect energy metabo- lism in breast cancer cells. In tumor tissues such as breast cancer and head and neck tumors, the expression of one of the mitomiRs (miR-210) correlates with hypoxia gene signatures, suggesting a direct link between mitomiR expression and hypoxia in cancer. The miR-17/92 cluster has been shown to act as a key factor in metabolic reprogramming of tumors by regulating glycolytic and mitochondrial metabolism. This cluster is deregulated in B-cell lymphomas, B-cell chronic lymphocytic leukemia, acute myeloid leukemia, and T-cell lymphomas, and is particularly overexpressed in several other cancers. Based on the current knowledge, we can conclude that there is a large number of miRNAs present in mitochondria, termed mitomiR, and that they are important regulators of mitochondrial function. Therefore, mitomiRs are important players in the metabolism of cancer cells, which need to be further investigated in order to develop a potential new therapies for cancer.
Ključne besede: microRNAs, mitomiR, mitochondria, cancer cell metabolism
Objavljeno v DiRROS: 22.07.2024; Ogledov: 332; Prenosov: 116
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