The Effects of a Mitochondrial Targeted Peptide (Elamipretide/SS31) on BAX Recruitment and Activation During Apoptosis

Abstract

Objective: Elamipretide (SS31) is a mitochondria-targeted peptide that has reported functions of stabilizing mitochondrial cristae structure and improving mitochondrial bioenergetics. Several studies have documented cell protective features of this peptide, including impairment of intrinsic apoptosis by inhibiting the recruitment and activation of the pro-apoptotic BAX protein. We used live-cell imaging of ARPE-19 cells expressing fluorescently labeled BAX, cytochrome c, and a mitochondrial marker to investigate the effect of elamipretide on the kinetics of BAX recruitment, mitochondrial outer membrane permeabilization (as a function of cytochrome c release), and mitochondrial fragmentation, respectively. Result: In nucleofected and plated ARPE-19 cells, elamipretide accelerated the formation of larger mitochondria. In the presence of the apoptotic stimulator, staurosporine, cells treated with elamipretide exhibited moderately slower rates of BAX recruitment. Peptide treatment, however, did not significantly delay the onset of BAX recruitment or the final total amount of BAX that was recruited. Additionally, elamipretide showed no impairment or delay of cytochrome c release or mitochondrial fragmentation, two events associated with normal BAX activation during cell death. These results indicate that the protective effect of elamipretide is not at the level of BAX activity to induce pro-apoptotic mitochondrial dysfunction after the initiation of staurosporine-induced apoptosis.

Common methods in mitochondrial research (Review)

“…SS31 and mitoTEMPO are novel mitochondrial-targeted antioxidants that have a scavenging effect on ROS (443)(444)(445)(446). In addition, SS31 accumulates in the mitochondrial membrane to protect and restore the mitochondrial structure without affecting healthy mitochondria (162,(447)(448)(449)(450)(451)(452)(453). Thus, SS31 and mitoTEMPO have protective effects on a variety of diseases, including heart and kidney-related diseases, as well as sepsis and diabetes, which have been demonstrated in a variety of animal models (454)(455)(456)(457).…”

Mitochondrial mutations and sterility in the interspecific hybrids of the hermaphroditic Argopecten scallops

“…In most cases, the functions of mitochondrial genes required the participation of nuclear genes, especially those genes involved in the respiratory chain and electron transport of mitochondria. Similarly, sterility may also be induced through the regulation of nuclear genes involved in critical pathways such as cell death and apoptosis by mitochondrial genes (Butow and Avadhani, 2004;Lam, 2004;Ouyang et al , 2010;Chen and Liu, 2014;Grosser et al , 2021). Thus, mitochondria may play an important role in sterility of interspecific F 1 hybrid scallops.…”