ミトコンドリア病

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge with limited therapeutic options. To identify new regulators of lipid metabolism, we developed a novel proteomic strategy combining organelle enrichment with a custom sORF database to explore the "dark proteome". Using this approach, we discovered MNP33, a previously uncharacterized 28-amino acid microprotein. This novel protein protects against metabolic disease in mice by potently reducing body weight gain, improving glucose homeostasis, and decreasing hepatic triacylglycerol (TAG) accumulation. Mechanistically, MNP33 localizes to the inner mitochondrial membrane, interacts with adenine nucleotide translocase 2 (ANT2), and induces a bioenergetic remodeling characterized by increased proton leak, elevated basal respiration, and a paradoxically elevated membrane potential. This promotion of energy dissipation provides a direct basis for the observed reduction in TAG. Our findings establish MNP33 as a key regulator of hepatic lipid metabolism with therapeutic potential for treating MASLD.

Vitiligo is a common cutaneous depigmentation disorder with a complex pathogenesis involving multiple factors such as oxidative stress, immune response, and metabolic disorders. Recent studies have revealed that the impaired energy metabolism in immune cells is closely linked to the pathogenesis of vitiligo, with mitochondrial homeostasis disruption playing a central role. Mitochondria not only serve as the cellular energy hub but also critically regulate immune cell function and activity. Furthermore, T cells have been shown to play pivotal roles in the development of vitiligo. This review systematically summarizes the multidimensional regulatory mechanisms underlying mitochondrial dysfunction and immune cell metabolic imbalance in the onset and progression of vitiligo. It highlights recent advances in precision treatment and targeted interventions, evaluating the progress and limitations of current mitochondria-oriented strategies, including antioxidants, mitochondrial protectants, metabolic modulators, and genetic therapies. We further propose the concept of "mitochondrial phenotype-based stratification", emphasizing the future integration of multi-omics data and functional assessments to achieve layered precision therapy for vitiligo. This work aims to offer novel insights and a theoretical foundation for the development of new treatment strategies and drug discovery in vitiligo.

Mitochondrial dysfunction represents a common pathological hub in tumors, neurodegenerative diseases, cardiovascular diseases, and inflammatory degenerative diseases. Nanozymes offer new opportunities for precision intervention. However, inadequate targeting and uncontrollable activity remain major obstacles to their clinical translation. This review proposes a "trinity" synergistic design paradigm, which exploits pathological mitochondrial signals as dual-functional cues for both subcellular navigation and catalytic activation, thereby achieving temporal coupling of "targeting enrichment" and "responsive activation." Within this framework, we first summarize the three major categories of nanozyme material systems and their mitochondrial targeting strategies. Subsequently, we systematically analyze the structural design and activation mechanisms of endogenous, exogenous, and multi-stimulus synergistic responsive nanozymes. We also establish a cross-scale effect chain model that cascades from catalytic events to mitochondrial metabolic remodeling, programmed cell death, and immune regulation. On this basis, we comprehensively review the therapeutic applications of these nanozymes in oncology, neurological disorders, cardiovascular diseases, and inflammatory degenerative diseases. Finally, we analyze the critical challenges confronting this field and provide perspectives on future directions, with the aim of offering theoretical references and research ideas for the development of mitochondria-targeted intelligent nanomedicines.

Bacterial pneumonia treatment faces significant challenges due to uncontrolled inflammation and rising antibiotic resistance. Excessive inflammatory cytokine release and mitochondrial dysfunction exacerbate tissue damage, contributing to the disease's progression. Mitophagy, a process that eliminates dysfunctional mitochondria, helps regulate reactive oxygen species (ROS) levels and suppress inflammation. However, efficient bacteria clearance remains critical for effective inflammatory modulation. Traditional antibiotics struggle against resistant bacteria, necessitating alternative approaches. ROS-based nanocatalytic therapies, particularly nanozymes, show potential for overcoming ROS generation limitations through external stimuli like ultrasound and magnetic fields. This study designs a sono-magneto-responsive nanozyme (BN@NF) composed of boron nanosheets (BN) and neodymium-doped iron phosphide (Nd:Fe2P, NF), modified to form a Z-scheme heterostructure. Delivered via nebulization, BN@NF generates ROS under combined internal and external stimuli, enabling efficient bacterial killing and biofilm disruption. It also modulates inflammation by inhibiting the NF-κB pathway and promoting mitophagy, reducing pro-inflammatory cytokine release. Additionally, BN@NF enhances macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, aiding tissue repair. This approach provides a promising strategy for treating bacterial pneumonia by combining effective antibacterial action with intelligent anti-inflammatory functions.

Morin (3,5,7,2',4'-pentahydroxyflavone) is a dietary flavonol with broad neuroprotective, anti-inflammatory, and antioxidant actions across central and peripheral nervous system models. This synthesis consolidates evidence from in vitro and rodent studies-covering neurodegenerative proteinopathies (Alzheimer's, Parkinson's, and Huntington's), neuropathic pain, epilepsy, stress- and schizophrenia-like phenotypes, and chemo-/toxicant-induced neurotoxicity-to evaluate morin's consistent benefits on survival, motor/cognitive performance, and biochemical normalization. Morin mitigated neurotoxicity induced by doxorubicin, ifosfamide, vincristine, acrylamide, heavy metals, and endocrine disruptors. Context-specific effects included modulation of disease-defining pathways (GSK3β/CDK5, mTORC1, PARP, and AMPK-ULK1-TFEB), microglial polarization, and normalization of neurotransmission (dopamine, GABA, 5-HT, and reduced AChE). Core mechanisms included the following: restoration of redox and mitochondrial homeostasis via Nrf2/HO-1 activation; replenishment of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH); decreased reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO); and preserved mitochondrial potential/fusion; suppression of innate immune and inflammasome signaling through downregulation of TLR4/NF-κB and ERK-p65, reduced TNF-α, IL-1β/IL-6, iNOS/COX-2; inhibition of NLRP3/caspase-1; and rebalancing of cell-death programs (↓Bax/caspase-3, ↑Bcl-2; attenuation of RIPK1/RIPK3/MLKL-mediated necroptosis). Formulation strategies (intranasal microemulsions, pluronic micelles, and more soluble derivatives) have enhanced brain exposure and efficacy, but translation now warrants optimized delivery, pharmacokinetic-pharmacodynamic mapping, target engagement biomarkers, and rigorously controlled trials to define dose, route, and indications as adjunctive to standard care in neurodegeneration, neuropathic pain, and toxicant-related brain injury. Collectively, morin emerges as a multitarget neuroprotective scaffold with reproducible functional and mechanistic benefits.