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Mitochondria contain connexins, a family of proteins that is known to form gap junction channels. Connexins are synthesized in the endoplasmic reticulum and oligomerized in the Golgi to form hemichannels. Hemichannels from adjacent cells dock with one another to form gap junction channels that aggregate into plaques and allow cell–cell communication. Cell–cell communication was once thought to be the only function of connexins and their gap junction channels. In the mitochondria, however, connexins have been identified as monomers and assembled into hemichannels, thus questioning their role solely as cell–cell communication channels. Accordingly, mitochondrial connexins have been suggested to play critical roles in the regulation of mitochondrial functions, including potassium fluxes and respiration. However, while much is known about plasma membrane gap junction channel connexins, the presence and function of mitochondrial connexins remain poorly understood. In this review, the presence and role of mitochondrial connexins and mitochondrial/connexin-containing structure contact sites will be discussed. An understanding of the significance of mitochondrial connexins and their connexin contact sites is essential to our knowledge of connexins’ functions in normal and pathological conditions, and this information may aid in the development of therapeutic interventions in diseases linked to mitochondria.
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Connectosomes for Direct Delivery of siRNA into the Cytoplasm.
Introduction: The plasma membrane protects a cell from the extracellular environment. As such it presents an obstacle that therapeutics needs to traverse in order to achieve efficacy. For example, small interfering RNAs (siRNAs) need to be delivered to the cytoplasm, where they can interact with the RNA interference machinery and initiate gene silencing. However, these macromolecules have poor membrane permeability, largely limiting their therapeutic potential. To address this challenge, current strategies involve encapsulating siRNAs into nanoparticles. However, upon cellular uptake, these nanoparticles are trapped in endosomes, which lack access to the cytoplasm. Towards developing an alternative strategy that provides direct access to the cytoplasm, we have been inspired by the unique capabilities of gap junctions to establish passageways between the cytoplasm of neighboring cells. Specifically, six connexins hexamerize to form a connexon hemichannel. Two hemichannels from neighboring cells dock to each other to form a complete gap junction channel, facilitating the exchange of molecular cargoes such as ions and siRNA. Therefore, incorporating the gap junction network into therapeutic delivery materials has the potential to enhance the delivery efficiency of siRNAs by directly depositing siRNAs into the cytoplasm.
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- Award ID(s):
- 1757885
- PAR ID:
- 10138554
- Date Published:
- Journal Name:
- 2019 BMES Conference Proceedings - REU Abstract Accepted Poster
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Conference Paper:
- The DOI is not currently available.
