Mitochondrial outer membrane permeabilization (MOMP) is a core event in apoptosis signaling. However, the underlying mechanism of BAX and BAK pore formation remains incompletely understood. We ...demonstrate that mitochondria are globally and dynamically targeted by endolysosomes (ELs) during MOMP. In response to pro-apoptotic BH3-only protein signaling and pharmacological MOMP induction, ELs increasingly form transient contacts with mitochondria. Subsequently, ELs rapidly accumulate within the entire mitochondrial compartment. This switch-like accumulation period temporally coincides with mitochondrial BAX clustering and cytochrome c release. Remarkably, interactions of ELs with mitochondria control BAX recruitment and pore formation. Knockdown of Rab5A, Rab5C, or USP15 interferes with EL targeting of mitochondria and functionally uncouples BAX clustering from cytochrome c release, while knockdown of the Rab5 exchange factor Rabex-5 impairs both BAX clustering and cytochrome c release. Together, these data reveal that EL-mitochondrial inter-organelle communication is an integral regulatory component of functional MOMP execution during cellular apoptosis signaling.
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•EL targeting of mitochondria is a common feature during apoptosis signaling•Knockdown of Rab5 or USP15 uncouples BAX clustering from MOMP•Rab5 GEF Rabex-5 regulates MOMP upstream of BAX recruitment•EL transformation of mitochondria positively regulates BAX-mediated MOMP
Wang et al. show that upon activation of regulated cell death, endolysosomal vesicles (ELs) are targeted to mitochondria prior to and during their permeabilization by BAX-mediated pores. These inter-organelle interactions result in a biochemical transformation of mitochondrial membranes and are required for functional in situ apoptotic pore formation.
The main objective was to increase the applicability of palygorskite by palygorskite sheets using a tape casting method. The stability of the suspension was investigated and the tapes were ...characterized by TGA/DTA, XRD, and SEM‐FEG. The antimicrobial activity was analyzed in order to test the applicability of a newly modified drug release system that incorporates neomycin in palygorskite. Preliminary results showed that the palygorskite sheet prepared via the tape casting is promising for wound healing applications.
Encapsulation is a valuable strategy to protect and deliver anthocyanins (ACNs), phenolic compounds with outstanding antioxidant capacity but limited stability. In this study, coacervation was used ...to encapsulate an ACN-rich red cabbage extract (RCE). Two agri-food by-product polymers, whey protein isolate (WPI) and apple high-methoxyl pectin (HMP), were blended at pH 4.0 in a specific ratio to induce the formation of nanoparticles (NPs). The process optimisation yielded a monodispersed population (PDI < 0.200) of negatively charged (−17 mV) NPs with an average diameter of 380 nm. RCE concentration influenced size, charge, and antioxidant capacity in a dose-dependent manner. NPs were also sensitive to pH increases from 4 to 7, showing a progressive breakdown. The encapsulation efficiency was 30%, with the retention of ACNs within the polymeric matrix being influenced by their chemical structure: diacylated and/or C3-triglucoside forms were more efficiently encapsulated than monoacylated C3-diglucosides. In conclusion, we report a promising, simple, and sustainable method to produce monodispersed NPs for ACN encapsulation and delivery. Evidence of differential binding of ACNs to NPs, dependent on specific acylation/glycosylation patterns, indicates that care must be taken in the choice of the appropriate NP formulation for the encapsulation of phenolic compounds.
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