mitochondrion

Overview

The mitochondrion (plural: mitochondria) is a double-membrane-bound organelle found in the cytoplasm of virtually all eukaryotic cells, widely recognized as the primary site of cellular energy production. Through the process of oxidative phosphorylation (OXPHOS), mitochondria convert nutrients into adenosine triphosphate (ATP), the universal energy currency of the cell. Beyond energy metabolism, mitochondria serve as central regulators of redox homeostasis, calcium signaling, programmed cell death (apoptosis), and cellular senescence. Their outer membrane contains specialized transmembrane β-barrel proteins that function as molecular gatekeepers, a structural feature shared with the outer membranes of Gram-negative bacteria and chloroplasts — a reflection of their endosymbiotic evolutionary origin. Critically, mitochondria harbor their own genome (mitochondrial DNA, or mtDNA), a circular chromosome encoding essential components of the respiratory chain, which is maintained under strict nuclear control and exists in multiple copies per cell, giving rise to phenomena such as heteroplasmy.

Mitochondria are now understood to be far more than static powerhouses. They form dynamic networks that undergo continuous fusion and fission, communicate with other organelles including the endoplasmic reticulum and lysosomes, and can even transfer between cells via tunneling nanotubes, extracellular vesicles, and as free organelles. Disruption of these functions — through oxidative stress, epigenetic dysregulation, impaired mitophagy, or mtDNA mutation — underlies a broad spectrum of human disease, including cardiovascular disease, neurodegeneration, cancer, chronic renal insufficiency, and age-related disorders. This central pathophysiological role has made mitochondria one of the most intensively studied targets in modern biomedical research and drug delivery science.

Focus of Latest Publications

Recent publications have continued to position the mitochondrion as a central therapeutic target in diverse disease settings, especially where metabolic reprogramming, oxidative stress, and cell death pathways are involved. In osteoarthritis, semaglutide was reported to improve mitochondrial metabolic disorders in muscle tissue in mice, with multi-omics analyses indicating that it targeted muscle mitochondria to regulate glutamine metabolism. The study further showed that mitochondria from semaglutide-stimulated C2C12 cells alleviated pain and cartilage damage, apparently by inhibiting muscle glutaminase activity and increasing circulating glutamine, which in turn reduced chondrocyte inflammation. This work highlights a muscle–cartilage axis in which mitochondrial regulation influences joint disease.

Several recent studies also used mitochondria as a focal site for nanomedicine-based interventions. In colitis, a ROS-responsive β-elemene nanoemulsion was shown to aggregate at mitochondrial sites in inflammatory macrophages, where it disrupted the electron transport chain, suppressed oxidative phosphorylation, and reprogrammed energy metabolism, leading to reduced M1 polarization and lower pro-inflammatory cytokine secretion. In cancer therapy, multiple approaches aimed to intensify mitochondrial stress: a glutathione-depleting nanodrug combined mitochondria-targeting photodynamic therapy with cuproptosis to induce mitochondrial dysfunction, immunogenic cell death, and immune activation; another DNA logic circuit-equipped redox amplifier formed DNA aggregates on mitochondria to disrupt membrane potential, increase ROS, and promote ferroptosis and cuproptosis; and a near-infrared-gated nanogenerator delivered nitric oxide and phototherapy to generate ROS/RNS that targeted mitochondria, causing membrane depolarization and ATP depletion.

Mitochondrial dysfunction was also a recurring theme in neurodegenerative disease research. In Alzheimer’s disease, near-infrared carbon dots were reported to selectively target mitochondria and preserve membrane potential under Beta amyloid- and copper(2+)-related oxidative challenge, while also suppressing Beta amyloid aggregation and scavenging reactive oxygen species. In Parkinson’s disease-related work, alpha-synuclein fibrils were found to damage mitochondrial cristae and enhance budding of mitochondrial-derived vesicles, suggesting a link between Synuclein alpha aggregation and mitochondrial quality-control responses. A separate proteomics and network analysis study in Alzheimer’s disease found that mitochondria protein modules were decreased in asymptomatic and symptomatic cases compared with controls, supporting broader mitochondrial involvement in disease progression.

Beyond disease-specific targeting, several studies focused on restoring or transferring mitochondrial function. In ischemic stroke, mitochondrial transcellular transfer through tunneling nanotubes, gap junctions, and extracellular vesicles was described as a mechanism that can reduce oxidative stress, improve neuronal energy metabolism, regulate neuroinflammation, and promote repair after cerebral ischemia-reperfusion injury. In kidney disease, mitochondrial transplantation was reviewed as a strategy to deliver viable, respiratory-competent mitochondria to injured tissue, with preclinical studies showing improved kidney function, reduced inflammation, and preserved mitochondrial structure. Related regenerative approaches also appeared in stroke therapy, where a piezocatalytic hydrogel was reported to target and repair mitochondria after ultrasound activation, suppress anaerobic metabolism, and reduce ischemic neurological dysfunction.

Key Publications

• NEWJun Semaglutide targets muscle mitochondria to regulate glutamine metabolism and treat osteoarthritis. (iScience, 2026, PMID 42305583): "The results of multi-omics analysis indicated that semaglutide targeted muscle mitochondria to regulate glutamine metabolism during OA."
• NEWJan ROS-Triggered Self-Aggregation of a β-Elemene Olefin-Rich Nanoemulsion for Mitochondrial-Targeted Metabolic Reprogramming and Colitis Inflammation Alleviation. (International journal of nanomedicine, 2026, PMID 42292035): "Mechanistically, upon reaching inflammatory macrophages, ELE-NE utilized the pathological ROS surge to undergo spatially confined aggregation at mitochondrial sites."
• NEWJan Autophagy-ferroptosis crosstalk in sepsis: metabolic pathways, redox injury, and host-directed antioxidant nanomedicine. (Frontiers in immunology, 2026, PMID 42282965): "Building on this framework, we evaluated emerging antioxidant nanomedicines targeting key intervention points, including iron chelation, catalytic ROS/RNS scavenging, membrane-localised radical trapping, mitochondria-targeted source control, and enhancement of endogenous defences."
• NEWJun Alpha-synuclein fibrils induce budding of mitochondrial-derived vesicles. (Proceedings of the National Academy of Sciences of the United States of America, 2026, PMID 42258734): "Our results suggest that α-syn may promote MDV generation, and support an important link between α-syn and mitochondria which will be important for future mechanistic studies."
• Apr [Mechanism of mitochondrial transcellular transfer in cerebral ischemia-reperfusion injury]. (Sheng li xue bao : [Acta physiologica Sinica], 2026, PMID 42014329): "Mitochondria, as organelles, usually exist inside cells."
• Apr Five-in-One Neurodetoxification-Guardian-Type Near-Infrared Carbon Dots for Synergistic Blockade of Alzheimer's Disease Pathological Cascade. (Analytical chemistry, 2026, PMID 42003377): "NGN-CDs also show dose-dependent broad-spectrum antioxidant activity, effectively scavenging ROS and alleviating oxidative stress. They selectively target mitochondria and preserve membrane potential under H2O2 or Aβ-Cu2+ challenge, protecting neuronal organelles."
• Jun Glutathione-depleting mitochondria-targeting nanodrugs for stress amplification and immune activation via synergistic photodynamic therapy and cuproptosis. (Acta biomaterialia, 2026, PMID 42002062): "The released PpIX-TPP effectively targeted mitochondria, inducing PDT effects under laser irradiation, causing oxidative stress and further reducing GSH levels."
• Apr Therapeutic and mechanistic insights on mitochondrial transplantation in kidney disease. (Nature reviews. Nephrology, 2026, PMID 41981250): "Mitochondria for transplantation can be isolated from a variety of sources (autologous or allogeneic) without triggering an immune, autoimmune or inflammatory response, or a reaction to damage-associated molecular patterns."
• May A NIR-Gated Nanogenerator Enables Low-Dose Nitric Oxide-Potentiated Phototherapy. (Angewandte Chemie (International ed. in English), 2026, PMID 41972828): "This synergistic ROS/RNS surge targets mitochondria, inducing membrane depolarization and rapid ATP depletion to trigger apoptosis."
• Apr DNA Logic Circuit-Equipped Redox Imbalance Amplifier for Precise Mitochondrial Disruption and Efficient Cancer Therapy. (Analytical chemistry, 2026, PMID 41952381): "The released DNA logic circuit response to these inputs can form DNA aggregates on the mitochondria, thus resulting in a cascade of mitochondrial membrane potential disruption and promoting reactive oxygen species (ROS) generation."