The release of mitochondrial reactive oxygen species (mROS) has been associated with oxidative stress, resulting in cellular dysfunction. Conversely, several studies have indicated that mROS can behave as a signaling molecule to regulate a variety of cellular functions. Our recent findings show that hydrogen peroxide, a byproduct of cellular respiration, is released from presynaptic mitochondria to promote activity-dependent, short-term plasticity (Stavrovskaya et al. 2025). It is unclear as how H 2 O 2 is released from mitochondria, as its high polarity restricts diffusion across lipid bilayers. This prompts several questions, with a main focus on the mechanisms by which H 2 O 2 is released from these organelles. We and others hypothesize that peroxiporins expressed in the inner membrane of the brain, liver, pancreas, and spermatozoa may form the pathway for release. It should be noted that there is no direct demonstration of the release of H 2 O 2 through the mitochondrial inner membrane, and the release pathway remains to be identified. Here, we adapted a method to measure the H 2 O 2 transport in synthetic liposomes by spectrofluorometric analysis (Wang et al. 2020). We found that, unlike in controls, liposomes fused with mitochondrial inner membranes had aquaporin-dependent transport as evidenced by inhibition with HgCl 2 and anti-aquaporin-8 antibodies. We further confirmed by fluorescence microscopy that aquaporin-8 partially localizes in mitochondria along with the inner membrane marker ATP5a protein. This is the first study to directly measure H 2 O 2 transport across the inner mitochondrial membrane, possibly though aquaporin 8.
Lebron et al. (2026) studied this question.