bims-smemid 2024-02-04 papers

Redox Biol. 2024 Jan 20. pii: S2213-2317(24)00025-9. [Epub ahead of print]70 103049

Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics.

Marissa D Pokharel, Alejandro Garcia-Flores, David Marciano, Maria C Franco, Jeffrey R Fineman, Saurabh Aggarwal, Ting Wang, Stephen M Black.

Once thought of in terms of bioenergetics, mitochondria are now widely accepted as both the orchestrator of cellular health and the gatekeeper of cell death. The pulmonary disease field has performed extensive efforts to explore the role of mitochondria in regulating inflammation, cellular metabolism, apoptosis, and oxidative stress. However, a critical component of these processes needs to be more studied: mitochondrial network dynamics. Mitochondria morphologically change in response to their environment to regulate these processes through fusion, fission, and mitophagy. This allows mitochondria to adapt their function to respond to cellular requirements, a critical component in maintaining cellular homeostasis. For that reason, mitochondrial network dynamics can be considered a bridge that brings multiple cellular processes together, revealing a potential pathway for therapeutic intervention. In this review, we discuss the critical modulators of mitochondrial dynamics and how they are affected in pulmonary diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), acute lung injury (ALI), and pulmonary arterial hypertension (PAH). A dysregulated mitochondrial network plays a crucial role in lung disease pathobiology, and aberrant fission/fusion/mitophagy pathways are druggable processes that warrant further exploration. Thus, we also discuss the candidates for lung disease therapeutics that regulate mitochondrial network dynamics.

Keywords: Mitochondrial function; Mitochondrial remodeling; Mitophagy; Pulmonary disease

DOI: https://doi.org/10.1016/j.redox.2024.103049

J Chromatogr A. 2024 Jan 28. pii: S0021-9673(24)00064-5. [Epub ahead of print]1717 464691

In-vivo tracking of deuterium metabolism in mouse organs using LC-MS/MS.

Siva Swapna Kasarla, Vera Flocke, Nay Min Thaw Saw, Antonia Fecke, Albert Sickmann, Matthias Gunzer, Ulrich Flögel, Prasad Phapale.

Mass spectrometry-based metabolomics with stable isotope labeling (SIL) is an established tool for sensitive and precise analyses of tissue metabolism, its flux, and pathway activities in diverse models of physiology and disease. Despite the simplicity and broad applicability of deuterium (2H)-labeled precursors for tracing metabolic pathways with minimal biological perturbations, they are rarely employed in LC-MS/MS-guided metabolomics. In this study, we have developed a LC-MS/MS-guided workflow to trace deuterium metabolism in mouse organs following 2H7 -glucose infusion. The workflow includes isotopically labeled glucose infusion, mouse organ isolation and metabolite extraction, zwitterion-based hydrophilic interaction liquid chromatography (HILIC) coupled to high-resolution tandem mass spectrometry, targeted data acquisition for sensitive detection of deuterated metabolites, a spectral library of over 400 metabolite standards, and multivariate data analysis with pathway mapping. The optimized method was validated for matrix effects, normalization, and quantification to provide both tissue metabolomics and tracking the in-vivo metabolic fate of deuterated glucose through key metabolic pathways. We quantified more than 100 metabolites in five major mouse organ tissues (liver, kidney, brain, brown adipose tissue, and heart). Furthermore, we mapped isotopologues of deuterated metabolites from glycolysis, tricarboxylic acid (TCA) cycle, and amino acid pathways, which are significant for studying both health and various diseases. This study will open new avenues in LC-MS based analysis of 2H-labeled tissue metabolism research in animal models and clinical settings.

Keywords: Deuterium tracing; LC-MS; Metabolic flux; Metabolomics; Tissue metabolism

DOI: https://doi.org/10.1016/j.chroma.2024.464691

Neurotherapeutics. 2024 Jan 30. pii: S1878-7479(24)00011-4. [Epub ahead of print]21(1): e00325

Biomarkers of mitochondrial disorders.

Brian J Shayota.

Mitochondrial diseases encompass a heterogeneous group of disorders with a wide range of clinical manifestations, most classically resulting in neurological, muscular, and metabolic abnormalities, but having the potential to affect any organ system. Over the years, substantial progress has been made in identifying and characterizing various biomarkers associated with mitochondrial diseases. This review summarizes the current knowledge of mitochondrial biomarkers based on a literature review and discusses the evidence behind their use in clinical practice. A total of 13 biomarkers were thoroughly reviewed including lactate, pyruvate, lactate:pyruvate ratio, creatine kinase, creatine, amino acid profiles, glutathione, malondialdehyde, GDF-15, FGF-21, gelsolin, neurofilament light-chain, and circulating cell-free mtDNA. Most biomarkers had mixed findings depending on the study, especially when considering their utility for specific mitochondrial diseases versus mitochondrial conditions in general. However, in large biomarker comparison studies, GDF-15 followed by FGF-21, seem to have the greatest value though they are still not perfect. As such, additional studies are needed, especially in light of newer biomarkers that have not yet been thoroughly investigated. Understanding the landscape of biomarkers in mitochondrial diseases is crucial for advancing early detection, improving patient management, and developing targeted therapies.

Keywords: Biomarker; Mitochondrial disease; Mitochondrial dysfunction

DOI: https://doi.org/10.1016/j.neurot.2024.e00325

J Exp Bot. 2024 Feb 02. 75(3): 663-666

Please, carefully, pass the P5C.

Paul E Verslues.

Keywords: Metabolic channelling; P5C dehydrogenase; mitochondria; ornithine aminotransferase; proline dehydrogenase; stress response

DOI: https://doi.org/10.1093/jxb/erad446