Mitochondrial dynamics including morphological fission and mitochondrial movement are essential to normal mitochondrial and cellular physiology. This study investigated how mtDNA T8993G (NARP)-induced inhibition of mitochondrial complex V altered mitochondrial dynamics in association with a protective mitochondrial phospholipid, cardiolipin (CL), as a potential therapeutic target. NARP cybrids harboring 98% of mtDNA T8993G genes and its parental osteosarcoma 143B cells were studied for comparison, and protection provided by melatonin, a potent mitochondrial protector, was explored. We demonstrate for the first time that NARP mutation significantly enhances apoptotic death as a result of three distinct lethal mitochondrial apoptotic insults including oxidative, Ca(2+), and lipid stress. In addition, NARP significantly augmented pathological depletion of CL. NARP-augmented depletion of CL results in enhanced retardation of mitochondrial movement and fission and later swelling of mitochondria during all insults. These results suggest that CL is a common and crucial pathological target for mitochondrial apoptotic insults. Furthermore, CL possibly plays a central role in regulating mitochondrial dynamics that are associated with NARP-augmented mitochondrial pathologies. Intriguingly, melatonin, by differentially preserving CL during various stresses (oxidation > Ca(2+) > lipid), rescues differentially CL-altered mitochondrial dynamics and cell death (oxidation > Ca(2+) > lipid). Thus, melatonin, in addition to being a mitochondrial antioxidant to antagonize mitochondrial oxidative stress, a mitochondrial permeability transition modulator to antagonize mitochondrial Ca(2+) stress, may stabilize directly CL to prevent its oxidization and/or depletion and, therefore, exerts great potential in rescuing CL-dependent mitochondrial dynamics-associated mitochondrial pathologies for treatment of NARP-induced pathologies and diseases.

Mitochondrial dysfunction is a hallmark of amyloid β-peptide (Aβ)-induced neurodegeneration of Alzheimer's disease (AD). This study investigated whether mtDNA T8993G mutation-induced complex V inhibition, clinically associated with neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP), is a potential risk factor for AD and the pathological link for long-term exposure of Aβ-induced mitochondrial toxicity and apoptosis in NARP cybrids. Using noninvasive fluorescence probe-coupled laser scanning imaging microscopy and NARP cybrids harboring 98% mutant genes along with its parental 143B osteosarcoma cells, we demonstrated that Aβ-augmented mitochondrial Ca(2+) (mCa(2+))-independent mitochondrial reactive oxygen species (mROS) formation for a cardiolipin (CL, a major mitochondrial protective phospholipid)-dependent lethal modulation of the mitochondrial permeability transition (MPT). Aβ augmented not only the amount but also the propagation rate of mROS-induced mROS formation to significantly depolarize mitochondrial membrane potential (∆Ψ(m)) and reduce mCa(2+) stress. Aβ-augmented mROS oxidized and depleted CL, thereby enhances mitochondrial fission and movement retardation, which promoted the NARP-augmented lethal transient-MPT (t-MPT) to switch to its irreversible mode of permanent-MPT (p-MPT). Interestingly, melatonin, a multiple mitochondrial protector, markedly reduced Aβ-augmented mROS formation and therefore significantly reduced mROS-mediated depolarization of ∆Ψ(m), fission of mitochondria and retardation of mitochondrial movement to stabilize CL and hence the MPT. In the presence of melatonin, Aβ-promoted p-MPT was reversed to a protective t-MPT, which preserved ∆Ψ(m) and lowered elevated mCa(2+) to sublethal levels for an enhanced mCa(2+)-dependent O(2) consumption. Thus, melatonin may potentially rescue AD patients associated with NARP symptoms.

Environmental-friendly nanocomposite hydrogels of carboxymethyl-hexanoyl chitosan (CHC), graphene oxide (GO) and cellulose nanocrystals (CNCs) were combined to produce a bio-hydrogel with great biocompatibility and antibacterial ability. The size of the GO nanosheets was about 200–500 nm, and the CNCs had a length of 100–200 nm and a width of 10–20 nm, as shown by transmission electron microscopy (TEM). X-ray photoelectron spectroscopy (XPS) was utilized for the analysis of the oxygen functional groups of GO. The homogeneous dispersion of the CHC/GO/CNC nanocomposite hydrogel showed significantly higher water absorption capacity and water retention capability. In addition, inhibition of a variety of microorganisms (gram-negative and gram-positive bacteria and fungi) by the introduction of the CHC/GO/CNC nanocomposite hydrogel demonstrated that there is a great opportunity to use it in the bio-medical field, such as for plastic masks and wound dressings.

Human induced pluripotent stem cells (hiPSCs) can be genetically reprogrammed to an embryonic stem cell-like state and can provide promising medical applications, such as diagnosis, prognosis, drug screening for therapeutical development, and monitoring disease progression. Despite myriad advances, traditional viral-based reprogramming for generating hiPSCs has safety risks that hinder further practical applications of hiPSCs. In the past decade, nonviral-based reprogramming has been used as an alternative to produce hiPSCs and enhance their differentiation. In addition, the efficiency of nonviral-based reprogramming is generally poor, compared to that of viral-based reprogramming. Recent studies in nanoscale-structured particles have made progress in addressing many applications of hiPSCs for clinical practice. The combination of hiPSCs and nanotechnology will actually act as the therapeutic platform for personalized medicine and can be the remedies against various diseases in the future. In this article, we review recent advances in cellular reprogramming and hiPSC-related research, such as cell source, delivery system, and direct reprogramming, as well as some of its potential clinical applications, including mitochondrial and retinal disease. We also briefly summarize the current incorporation of nanotechnology in patient-specific hiPSCs for future treatments.