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Mitochondrial dynamics are central to the pathophysiology of cellular damage and inflammatory responses. In the context of solid organ transplantation, mitochondria are implicated in immune activation in donor organs that occurs after brain death, as they are critical to the regulation of cellular stress response, cell death, and display energetic adaptations through the adjustment of respiratory capacity depending on the cellular milieu. Mitochondrial damage activates mitochondrial systems of fission, fusion, biogenesis, and mitochondrial autophagy, or mitophagy. The mechanistic pathways as well as therapies targeting mitochondrial physiology have been studied as plausible ways to mitigate the negative effects of brain death on donor organs, though there is no summative evaluation of the multiple efforts across the field. This mini-review aims to discuss the interplay of donor brain death, mitochondrial dynamics, and impact on allograft function as it pertains to heart, lung, liver, and kidney transplants.

Vitiligo is an autoimmune skin disease characterized by melanocyte destruction. Regulatory T cells (Tregs) are greatly reduced in vitiligo skin, and replenishing peripheral skin Tregs can provide protection against depigmentation. Ganglioside D3 (GD3) is overexpressed by perilesional epidermal cells, including melanocytes, which prompted us to generate GD3-reactive chimeric antigen receptor (CAR) Tregs to treat vitiligo. Mice received either untransduced Tregs or GD3-specific Tregs to test the hypothesis that antigen specificity contributes to reduced autoimmune reactivity in vitro and in vivo. CAR Tregs displayed increased IL-10 secretion in response to antigen, provided superior control of cytotoxicity towards melanocytes, and supported a significant delay in depigmentation compared to untransduced Tregs and vehicle control recipients in a TCR transgenic mouse model of spontaneous vitiligo. The latter findings were associated with a greater abundance of Tregs and melanocytes in treated mice versus both control groups. Our data support the concept that antigen-specific Tregs can be prepared, used, and stored for long-term control of progressive depigmentation.

Cationic liposomes are widely used to facilitate introduction of genetic material into target cells during transfection. This study describes a non-receptor mediated herpes simplex virus type-1 (HSV-1) entry into the Chinese hamster ovary (CHO-K1) cells that naturally lack glycoprotein D (gD)-receptors using a commercially available cationic liposome: lipofectamine. Presence of cell surface heparan sulfate (HS) increased the levels of viral entry indicating a potential role of HS in this mode of entry. Loss of viral entry in the presence of actin de-polymerizing or lysosomotropic agents suggests that this mode of entry results in the endocytosis of the lipofectamine-virus mixture. Enhancement of HSV-1 entry by liposomes was also demonstrated in vivo using a zebrafish embryo model that showed stronger infection in the eyes and other tissues. Our study provides novel insights into gD receptor independent viral entry pathways and can guide new strategies to enhance the delivery of viral gene therapy vectors or oncolytic viruses.