MSL1 is a mechanosensitive ion channel that dissipates mitochondrial membrane potential and maintains redox homeostasis in mitochondria during abiotic stress

Abstract

Mitochondria must maintain tight control over the electrochemical gradient across their inner membrane to allow ATP synthesis while maintaining a redox-balanced electron transport chain and avoiding excessive reactive oxygen species production. However, there is a scarcity of knowledge about the ion transporters in the inner mitochondrial membrane that contribute to control of membrane potential. We show that loss of MSL1, a member of a family of mechanosensitive ion channels related to the bacterial channel MscS, leads to increased membrane potential of Arabidopsis mitochondria under specific bioenergetic states. We demonstrate that MSL1 localises to the inner mitochondrial membrane. When expressed in E. coli, MSL1 forms a stretch-activated ion channel with a slight preference for anions and provides protection against hypo-osmotic shock. In contrast, loss of MSL1 in Arabidopsis did not prevent swelling of isolated mitochondria in hypo-osmotic conditions. Instead, our data suggest that ion transport by MSL1 leads to dissipation of mitochondrial membrane potential when it becomes too high. The importance of MSL1 function was demonstrated by the observation of a higher oxidation state of the mitochondrial glutathione pool in msl1-1 mutants under moderate heat- and heavy-metal-stress. Furthermore, we show that MSL1 function is not directly implicated in mitochondrial membrane potential pulsing but is complementary and appears to be important under similar conditions.

Life behind the wall: sensing mechanical cues in plants

“…In general, MSL proteins appear to serve as tension-regulated osmotic safety valves [64, 65], although more complex roles have also been suggested [66–68]. The Mid1-complementing activity (MCA) proteins were identified by virtue of their ability to rescue a yeast Δmid1 phenotype.…”

Plant mechanosensitive ion channels: an ocean of possibilities

“…Electrophysiological analyses of MSL9 and MSL10 in plant cells [22], MSL10 and MSL8 expressed heterologously in Xenopus oocytes [23,24], and MSL1 expressed heterologously in giant E. coli spheroplasts [21] all revealed channel characteristics that are similar (though not identical) to Ec MscS. MSLs are anion-preferring (e.g.…”

“…While the pleiotropic phenotypes associated with this mutant have illustrated the importance of plastid osmoregulation during normal plant growth and development, any mechanistic insights await the electrophysiological analysis of MSL2 and MSL3—a challenging prospect for plastid-localized proteins. Adding to the complexity is a recent report demonstrating that mitochondria-localized MSL1 is required to ameliorate the oxidative burden imposed upon mitochondria during abiotic stress [21]. The potential role of membrane tension, redox state, and transmembrane voltage in regulating MSL1 channel activity in vivo remains to be determined.…”

Genome-Wide Association Mapping Reveals That Specific and Pleiotropic Regulatory Mechanisms Fine-Tune Central Metabolism and Growth in Arabidopsis

“…MSL family members act as osmotic safety valves to release osmolytes under increased membrane tension (Maksaev and Haswell, 2012). These proteins have been implicated in pollen development (Hamilton et al, 2015), osmotic regulation in plastids , redox homeostasis in mitochondria (Lee et al, 2016), and cell death (Veley et al, 2014). The link between MSL10, sugars, and starch metabolism might be related to osmotic and turgor regulation.…”