Air pollution exerts several deleterious effects on the cardiovascular system, with cardiovascular disease (CVD) accounting for 80% of all premature deaths caused by air pollution. Short-term exposure to particulate matter 2.5 (PM_2.5) leads to acute CVD-associated deaths and nonfatal events, whereas long-term exposure increases CVD-associated risk of death and reduces longevity. Here, we summarize published data illustrating how PM_2.5 may impact the cardiovascular system to provide information on the mechanisms by which it may contribute to CVDs. We provide an overview of PM_2.5, its associated health risks, global statistics, mechanistic underpinnings related to mitochondria, and hazardous biological effects. We elaborate on the association between PM_2.5 exposure and CVD development and examine preventive PM_2.5 exposure measures and future strategies for combating PM_2.5-related adverse health effects. The insights gained can provide critical guidelines for preventing pollution-related CVDs through governmental, societal, and personal measures, thereby benefitting humanity and slowing climate change.

Here we report the expansion of the genetic code of Mus musculus with various unnatural amino acids including N^ɛ-acetyl-lysine. Stable integration of transgenes encoding an engineered N^ɛ-acetyl-lysyl-tRNA synthetase (AcKRS)/tRNA^Pyl pair into the mouse genome enables site-specific incorporation of unnatural amino acids into a target protein in response to the amber codon. We demonstrate temporal and spatial control of protein acetylation in various organs of the transgenic mouse using a recombinant green fluorescent protein (GFPuv) as a model protein. This strategy will provide a powerful tool for systematic in vivo study of cellular proteins in the most commonly used mammalian model organism for human physiology and disease.

Regulation of mitochondrial DNA (mtDNA) expression is critical for the control of oxidative phosphorylation in response to physiological demand, and this regulation is often impaired in disease and aging. We have previously shown that mitochondrial transcription termination factor 3 (MTERF3) is a key regulator that represses mtDNA transcription in the mouse, but its molecular mode of action has remained elusive. Based on the hypothesis that key regulatory mechanisms for mtDNA expression are conserved in metazoans, we analyzed Mterf3 knockout and knockdown flies. We demonstrate here that decreased expression of MTERF3 not only leads to activation of mtDNA transcription, but also impairs assembly of the large mitochondrial ribosomal subunit. This novel function of MTERF3 in mitochondrial ribosomal biogenesis is conserved in the mouse, thus we identify a novel and unexpected role for MTERF3 in coordinating the crosstalk between transcription and translation for the regulation of mammalian mtDNA gene expression. One of the main functions of the mitochondrial network is to provide the energy currency ATP to drive a large array of cellular metabolic processes. The formation of the mitochondrial respiratory chain, which allows this energy supply, is under the control of two separate genetic systems, the nuclear and the mitochondrial genomes, whose expressions have to be tightly coordinated to ensure efficient mitochondrial function. The regulation of mitochondrial genome expression is still poorly understood despite the profound importance of this process in human physiology, disease, and aging. Here, we make one step forward by unraveling a new role for the mitochondrial transcription termination factor 3 (MTERF3), which was initially characterized as a factor able to decrease mitochondrial transcription. Using gene invalidation approaches, we show in two distinct model organisms, the fruit fly and the mouse, that MTERF3 is not only involved in mitochondrial transcription but also favors the assembly of the mitochondrial ribosome and thereby reinforces the coordination between transcription and translation events, two key steps in mitochondrial genome expression.

Yihyang Kim, Solomon Ergando Dube, and Chan Bae Park. Korean J Physiol Pharmacol 2025;29:1-8. https://doi.org/10.4196/kjpp.24.388

Nanoparticles are a useful material in biomedicine given their unique properties and biocompatibility; however, there is increasing concern regarding the potential toxicity of nanoparticles with respect to cell metabolism. Some evidence suggests that nanoparticles can disrupt glucose and energy homeostasis. In this study, we investigated the metabolomic, transcriptomic, and integrated effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO₂(RITC)] on glucose metabolism in human embryonic kidney 293 (HEK293) cells. Using gas chromatography–tandem mass spectrometry, we analysed the metabolite profiles of 14 organic acids (OAs), 20 amino acids (AAs), and 13 fatty acids (FAs) after treatment with 0.1 or 1.0 µg/µl MNPs@SiO₂(RITC) for 12 h. The metabolic changes were highly related to reactive oxygen species (ROS) generation and glucose metabolism. Additionally, effects on the combined metabolome and transcriptome or “metabotranscriptomic network” indicated a relationship between ROS generation and glucose metabolic dysfunction. In the experimental validation, MNPs@SiO₂(RITC) treatment significantly decreased the amount of glucose in cells and was associated with a reduction in glucose uptake efficiency. Decreased glucose uptake efficiency was also related to ROS generation and impaired glucose metabolism in the metabotranscriptomic network. Our results suggest that exposure to high concentrations of MNPs@SiO₂(RITC) produces maladaptive alterations in glucose metabolism and specifically glucose uptake as well as related metabolomic and transcriptomic disturbances via increased ROS generation. These findings further indicate that an integrated metabotranscriptomics approach provides useful and sensitive toxicological assessment for nanoparticles.

Neurons' high energy demands for processing, transmitting, and storing information in the brain necessitate efficient energy metabolism to maintain normal neuronal function. The astrocyte-neuron lactate shuttle (ANLS) hypothesis suggests neurons preferentially use lactate from astrocytes over glucose for energy. This study investigated lactate dehydrogenase B (LDHB), which preferentially converts lactate to pyruvate, in neuronal energy metabolism and cognitive function. LDHB-deficient neurons showed reduced lactate-driven energy metabolism in culture, while LDHB-deficient brains accumulated lactate, both indicating decreased lactate utilization. This reduced lactate utilization was correlated with impaired long-term memory in LDHB-deficient mice, while short-term memory remained unaffected and overall neuropathology was only mildly disturbed. Unexpectedly, LDHB-deficient neurons maintain stable energy metabolism under physiological glucose conditions, indicating the presence of lactate dehydrogenase (LDH) activity in LDHB-deficient neurons. The observation of lactate dehydrogenase A (LDHA), which preferentially converts pyruvate to lactate but can also catalyze the reverse reaction less efficiently, in LDHB-deficient neurons may explain their stable energy metabolism and reduced lactate utilization. This study challenges the established concept of strict LDH isoform compartmentalization in brain cells, questioning the exclusive presence of LDHB in neurons and suggesting a more flexible neuronal metabolic profile than previously assumed by the ANSL hypothesis.