A high density of tumor-associated macrophages (TAMs) is associated with poorer prognosis and survival in breast cancer patients. Recent studies have shown that lipid accumulation in TAMs can promote tumor growth and metastasis in various models. However, the specific molecular mechanisms that drive lipid accumulation and tumor progression in TAMs remain largely unknown.
View Article and Find Full Text PDFChronic inflammation contributes to the prevalence of cardiovascular disease in people living with HIV (PLWH). The immune mechanisms driving atherosclerosis progression in PLWH remain unclear. This study conducted comprehensive assessments of medium-sized coronary arteries and aorta from deceased PLWH and controls without HIV using DNA/RNA assays, spatial transcriptomics, and high-resolution mass spectrometry.
View Article and Find Full Text PDFAbdominal and thoracic aortic aneurysms (AAAs, TAAs) remain a major cause of deaths worldwide, in part due to the lack of reliable prognostic markers or early warning signs. Sox6 has been found to regulate renin controlling blood pressure. We hypothesized that Sox6 may serve as an important regulator of the mechanisms contributing to hypertension-induced aortic aneurysms.
View Article and Find Full Text PDFUnlabelled: A high density of tumor-associated macrophages (TAMs) is associated with poorer prognosis and survival in breast cancer patients. Recent studies have shown that lipid accumulation in TAMs can promote tumor growth and metastasis in various models. However, the specific molecular mechanisms that drive lipid accumulation and tumor progression in TAMs remain largely unknown.
View Article and Find Full Text PDFThe liver, the largest internal organ and a metabolic hub, undergoes significant declines due to aging, affecting mitochondrial function and increasing the risk of systemic liver diseases. How the mitochondrial three-dimensional (3D) structure changes in the liver across aging, and the biological mechanisms regulating such changes confers remain unclear. In this study, we employed Serial Block Face-Scanning Electron Microscopy (SBF-SEM) to achieve high-resolution 3D reconstructions of murine liver mitochondria to observe diverse phenotypes and structural alterations that occur with age, marked by a reduction in size and complexity.
View Article and Find Full Text PDFThe kidney filters nutrient waste and bodily fluids from the bloodstream, in addition to secondary functions of metabolism and hormone secretion, requiring an astonishing amount of energy to maintain its functions. In kidney cells, mitochondria produce adenosine triphosphate (ATP) and help maintain kidney function. Due to aging, the efficiency of kidney functions begins to decrease.
View Article and Find Full Text PDFThe sorting and assembly machinery (SAM) Complex is responsible for assembling β-barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity.
View Article and Find Full Text PDFMitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are protein- and lipid-enriched hubs that mediate interorganellar communication by contributing to the dynamic transfer of Ca, lipid, and other metabolites between these organelles. Defective MERCs are associated with cellular oxidative stress, neurodegenerative disease, and cardiac and skeletal muscle pathology via mechanisms that are poorly understood. We previously demonstrated that skeletal muscle-specific knockdown (KD) of the mitochondrial fusion mediator optic atrophy 1 (OPA1) induced ER stress and correlated with an induction of Mitofusin-2, a known MERC protein.
View Article and Find Full Text PDFAge-related atrophy of skeletal muscle, is characterized by loss of mass, strength, endurance, and oxidative capacity during aging. Notably, bioenergetics and protein turnover studies have shown that mitochondria mediate this decline in function. Although exercise has been the only therapy to mitigate sarcopenia, the mechanisms that govern how exercise serves to promote healthy muscle aging are unclear.
View Article and Find Full Text PDFICOS (Inducible T Cell Costimulator), one of the co-stimulatory B7 superfamily members, was characterized as a co-stimulatory receptor for T-cell enhancement. However, the role of ICOS in breast cancer remains largely unknown. The present study systematically investigated the expression pattern and its relation to clinical characteristics and immunotherapy by integrating multiple clinical cohorts and large-scale gene expression data.
View Article and Find Full Text PDFThis study, utilizing SBF-SEM, reveals structural alterations in mitochondria and myofibrils in human heart failure (HF). Mitochondria in HF show changes in structure, while myofibrils exhibit increased cross-sectional area and branching. Metabolomic and lipidomic analyses indicate concomitant dysregulation in key pathways.
View Article and Find Full Text PDFDuring aging, muscle gradually undergoes sarcopenia, the loss of function associated with loss of mass, strength, endurance, and oxidative capacity. However, the 3D structural alterations of mitochondria associated with aging in skeletal muscle and cardiac tissues are not well described. Although mitochondrial aging is associated with decreased mitochondrial capacity, the genes responsible for the morphological changes in mitochondria during aging are poorly characterized.
View Article and Find Full Text PDFIsolation of skeletal muscles allows for the exploration of many complex diseases. Here, we present a protocol for isolating mice skeletal muscle myoblasts and myotubes that have been differentiated through antibody validation. We describe steps for collecting and preparing murine skeletal tissue, myoblast cell maintenance, plating, and cell differentiation.
View Article and Find Full Text PDFThis review provides an overview of the current methods for quantifying mitochondrial ultrastructure, including cristae morphology, mitochondrial contact sites, and recycling machinery and a guide to utilizing electron microscopy to effectively measure these organelles. Quantitative analysis of mitochondrial ultrastructure is essential for understanding mitochondrial biology and developing therapeutic strategies for mitochondrial-related diseases. Techniques such as transmission electron microscopy (TEM) and serial block face-scanning electron microscopy, as well as how they can be combined with other techniques including confocal microscopy, super-resolution microscopy, and correlative light and electron microscopy are discussed.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
November 2023
With sparse treatment options, cardiac disease remains a significant cause of death among humans. As a person ages, mitochondria breakdown and the heart becomes less efficient. Heart failure is linked to many mitochondria-associated processes, including endoplasmic reticulum stress, mitochondrial bioenergetics, insulin signaling, autophagy, and oxidative stress.
View Article and Find Full Text PDFDeep-lake (reservoir) ecosystems provide valuable ecosystem services (ES) and generate significant ecosystem service values (ESV); however, reservoir ecosystems have suffered great losses from environmental changes and human activities. Currently, studies on ES and its correlations with stressors remain insufficient and the integration of ES into ecological restoration and management poses numerous challenges. Here, we combined four types of stressors with six ES closely related to human well-being to discuss their interactions in Qiandao Lake (a representative deep lake in China).
View Article and Find Full Text PDFDespite tremendous diversity, Asian Americans in STEM are grouped and viewed as a homogeneous monolith, facing stereotypes and disparities. We propose solutions that include disaggregating the Asian American grouping and recognizing the diverse individual ethnic subgroups that comprise Americans of Asian ancestry to implement change within the STEM field.
View Article and Find Full Text PDFIsolation of skeletal muscles allows for the exploration of many complex diseases. Fibroblasts and myoblast play important roles in skeletal muscle morphology and function. However, skeletal muscles are complex and made up of many cellular populations and validation of these populations is highly important.
View Article and Find Full Text PDFThe Sorting and Assembly Machinery (SAM) Complex is responsible for assembling β-barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system (MICOS) complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity.
View Article and Find Full Text PDFProximity ligation assays (PLA) use specific antibodies to detect endogenous protein-protein interactions. PLA is a highly useful biochemical technique that allows two proteins within close proximity to be visualized with fluorescent probes amplified by PCR. While this technique has gained prominence, the use of PLA in mouse skeletal muscle (SkM) is novel.
View Article and Find Full Text PDFOPA1 is a dynamin-related GTPase that modulates various mitochondrial functions and is involved in mitochondrial morphology. There are eight different isoforms of OPA1 in humans and five different isoforms in mice that are expressed as short or long-form isoforms. These isoforms contribute to OPA1's ability to control mitochondrial functions.
View Article and Find Full Text PDFMachine learning has proven useful in analyzing complex biological data and has greatly influenced the course of research in structural biology and precision medicine. Deep neural network models oftentimes fail to predict the structure of complex proteins and are heavily dependent on experimentally determined structures for their training and validation. Single-particle cryogenic electron microscopy (cryoEM) is also advancing the understanding of biology and will be needed to complement these models by continuously supplying high-quality experimentally validated structures for improvements in prediction quality.
View Article and Find Full Text PDFAn increased risk of cardiometabolic disease accompanies persistent systemic inflammation. Yet, the innate and adaptive immune system features in persons who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric and other immune phenotyping analyses, which limits our understanding of their relationship to disease states.
View Article and Find Full Text PDFMitochondria respond to metabolic demands of the cell and to incremental damage, in part, through dynamic structural changes that include fission (fragmentation), fusion (merging of distinct mitochondria), autophagic degradation (mitophagy), and biogenic interactions with the endoplasmic reticulum (ER). High resolution study of mitochondrial structural and functional relationships requires rapid preservation of specimens to reduce technical artifacts coupled with quantitative assessment of mitochondrial architecture. A practical approach for assessing mitochondrial fine structure using two dimensional and three dimensional high-resolution electron microscopy is presented, and a systematic approach to measure mitochondrial architecture, including volume, length, hyperbranching, cristae morphology, and the number and extent of interaction with the ER is described.
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