bims-mionch 2024-09-29 papers

Issue of 2024–09–29
four papers selected by
Gun Kim, Seoul National University

Exp Eye Res. 2024 Sep 24. pii: S0014-4835(24)00332-4. [Epub ahead of print] 110110

Current Insights on Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) and their significance in the pathophysiology of ocular disorders.

Xin-Yu Zhang, Cheng Han, Yong Yao, Ting-Ting Wei.

The intricate interaction network necessary for essential physiological functions underscores the interdependence among eukaryotic cells. Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs), specialized junctions between mitochondria and the ER, were recently discovered. These junctions participate in various cellular processes, including calcium level regulation, lipid metabolism, mitochondrial integrity maintenance, autophagy, and inflammatory responses via modulating the structure and molecular composition of various cellular components. Therefore, MAMs contribute to the pathophysiology of numerous ocular disorders, including Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD) and glaucoma. In addition to providing a concise overview of the architectural and functional aspects of MAMs, this review explores the key pathogenetic pathways involving MAMs in the development of several ocular disorders.

Keywords: Eye Diseases; Mitochondria-Associated Endoplasmic Reticulum Membranes; Pathophysiology

DOI: https://doi.org/10.1016/j.exer.2024.110110

J Lipid Res. 2024 Sep 18. pii: S0022-2275(24)00148-2. [Epub ahead of print] 100643

Setting the curve: the biophysical properties of lipids in mitochondrial form and function.

Kailash Venkatraman, Christopher T Lee, Itay Budin.

Mitochondrial membranes are defined by their diverse functions, complex geometries, and unique lipidomes. In the inner mitochondrial membrane (IMM), highly-curved membrane folds known as cristae house the electron transport chain and are the primary sites of cellular energy production. The outer mitochondrial membrane (OMM) is flat by contrast, but is critical for the initiation and mediation of processes key to mitochondrial physiology: mitophagy, inter-organelle contacts, fission and fusion dynamics and metabolite transport. While the lipid composition of both the IMM and OMM have been characterized across a variety of cell types, a mechanistic understanding for how individual lipid classes contribute to mitochondrial structure and function remains nebulous. In this review, we address the biophysical properties of mitochondrial lipids and their related functional roles. We highlight the intrinsic curvature of the bulk mitochondrial phospholipid pool, with an emphasis on the nuances surrounding the mitochondrially-synthesized cardiolipin. We also outline emerging questions about other lipid classes, ether lipids and sterols, with potential roles in mitochondrial physiology. We propose that further investigation is warranted to elucidate the specific properties of these lipids and their influence on mitochondrial architecture and function.

Keywords: Cardiolipin; Curvature; Mitochondria; Phospholipids; Plasmalogens; Sterols

DOI: https://doi.org/10.1016/j.jlr.2024.100643

Medicine (Baltimore). 2024 Sep 27. 103(39): e39158

Ferroptosis: Regulatory mechanisms and potential targets for bone metabolism: A review.

Yongjie Zhang, Kangyi Hu, Zhengya Shang, Xiaorui Yang, Linzhong Cao.

Bone homeostasis is a homeostasis process constructed by osteoblast bone formation and osteoclast bone resorption. Bone homeostasis imbalance and dysfunction are the basis for the development of various orthopedic diseases such as osteoporosis, osteoarthritis, and steroid-induced avascular necrosis of femoral head. Previous studies have demonstrated that ferroptosis can induce lipid peroxidation through the generation of reactive oxygen species, activate a number of signaling pathways, and participate in the regulation of osteoblast bone formation and osteoclast bone resorption, resulting in bone homeostasis imbalance, which is an important factor in the pathogenesis of many orthopedic diseases, but the mechanism of ferroptosis is still unknown. In recent years, it has been found that, in addition to iron metabolism and intracellular antioxidant system imbalance, organelle dysfunction is also a key factor affecting ferroptosis. This paper takes this as the starting point, reviews the latest literature reports at home and abroad, elaborates the pathogenesis and regulatory pathways of ferroptosis and the relationship between ferroptosis and various organelles, and summarizes the mechanism by which ferroptosis mediates bone homeostasis imbalance, with the aim of providing new directions for the research related to ferroptosis and new ideas for the prevention and treatment of bone and joint diseases.

DOI: https://doi.org/10.1097/MD.0000000000039158

Chem Commun (Camb). 2024 Sep 25.

Targeting sub-cellular organelles for boosting precision photodynamic therapy.

Gopal Singh Attar, Manoj Kumar, Vandana Bhalla.

Among various cancer treatment methods, photodynamic therapy has received significant attention due to its non-invasiveness and high efficiency in inhibiting tumour growth. Recently, specific organelle targeting photosensitizers have received increasing interest due to their precise accumulation and ability to trigger organelle-mediated cell death signalling pathways, which greatly reduces the drug dosage, minimizes toxicity, avoids multidrug resistance, and prevents recurrence. In this review, recent advances and representative photosensitizers used in targeted photodynamic therapy on organelles, specifically including the endoplasmic reticulum, Golgi apparatus, mitochondria, nucleus, and lysosomes, have been comprehensively reviewed with a focus on organelle structure and organelle-mediated cell death signalling pathways. Furthermore, a perspective on future research and potential challenges in precision photodynamic therapy has been presented at the end.

DOI: https://doi.org/10.1039/d4cc02702g