Lung epithelial endoplasmic reticulum and mitochondrial 3D ultrastructure: a new frontier in lung diseases

Abstract

It has long been appreciated that the endoplasmic reticulum (ER) and mitochondria, organelles important for regular cell function and survival, also play key roles in pathogenesis of various lung diseases, including asthma, fibrosis, and infections. Alterations in processes regulated within these organelles, including but not limited to protein folding in the ER and oxidative phosphorylation in the mitochondria, are important in disease pathogenesis. In recent years it has also become increasingly apparent that organelle structure dictates function. It is now clear that organelles must maintain precise organization and localization for proper function. Newer microscopy capabilities have allowed the scientific community to reveal, via 3D imaging, that the structure of these organelles and their interactions with each other are a main component of regulating function and, therefore, effects on the disease state. In this review, we will examine how 3D imaging through techniques could allow advancements in knowledge of how the ER and mitochondria function and the roles they may play in lung epithelia in progression of lung disease.

Heterogeneous Ribonucleoprotein A1 (hnRNPA1) Interacts with the Nucleoprotein of the Influenza a Virus and Impedes Virus Replication

“…Temporal distribution studies identified increased hnRNPA1-NP co-localization in the nuclear and mitochondrial compartments in NPtransfected and IAV-infected cells, thereby enhancing the possibility of interaction between the two. Mitochondrial accumulation of Influenza A vRNP is well documented as it is associated with the induction of interferon (IFN) and antiviral immune signaling [46][47][48][49][50]. On the other hand, hnRNPA1 is enriched in the nuclear and cytosolic fraction in response to various internal and external stimuli [51].…”

Mitochondrial Population in Mouse Eosinophils: Ultrastructural Dynamics in Cell Differentiation and Inflammatory Diseases

“…While TEM has the limitation of relying on static observations, it enables distinguishing between contiguous membranes and accurate quantification of mitochondrial morphology and interactions ( Picard et al, 2013 ). One of the most recognized of these mitochondrial interactions is with the ER within different cell types ( Csordás et al, 2006 ), including epithelial cells in the context of lung diseases [reviewed in ( Bruno and Anathy, 2021 )] and immune cells [reviewed in ( Angajala et al, 2018 )]. For example, in T cells, such interaction enables metabolic reprogramming necessary for immune responses ( Bantug et al, 2018 ).…”

In focus in HCB

“…For many years, Charavarymath and colleagues have been studying the mechanisms underlying pulmonary effects of exposure to airborne organic dusts (Bhat et al 2019;Charavarymath et al 2005Charavarymath et al , 2008Charavarymath and Singh 2006). They have now focussed their attention on mitochondria (Bhat et al 2021), and provide an extensive and detailed analysis of mitochondrial structure and function in cells treated with organic dust extract (ODE). Using cultured human monocytic cells (THP1) as an in vitro model representing human lung macrophages, they performed a wide variety of mitochondrial ultrastructural and physiological analyses, including cell viability and the MTT assay, mitochondrial DNA isolation, quantitative RT-PCR, Western blot analysis, mitochondrial activity via the MitoSOX assay, calcium influx measurements, nitric oxide secretion via the Griess assay, multi-cytokine identification, subcellular fractionation, and transmission electron microscopy followed by morphological image analysis.…”

“…tOS-NPs were prepared in 100 and 1000 nm size distributions, and then conjugated to either rhodamine B or fluorescein isothiocyanate (FITC). Animals were then administered intravaginally either size of the fluorescently tagged From Bhat et al (2021) tOS-NPs, or as a combination of the two different-sized particles. The distribution of the fluorescence signal was then determined in different areas of the genital tract, including the vagina, endometrium, and ovaries.…”

“…2 Organic dust extract (ODE) exposure induces selective targeting of mitochondria for autophagy (mitophagy) as indicated by increased Parkin protein amounts in cultured human monocytic cells. Co-exposure to ethyl pyruvate (EP) or mito-apocynin (MA) significantly reduced the increase in ODE exposure-induced Parkin protein.FromBhat et al (2021)…”