Clearing the outer mitochondrial membrane from harmful proteins via lipid droplets

Abstract

In recent years it turned out that there is not only extensive communication between the nucleus and mitochondria but also between mitochondria and lipid droplets (LDs) as well. We were able to demonstrate that a number of proteins shuttle between LDs and mitochondria and it depends on the metabolic state of the cell on which organelle these proteins are predominantly localized. Responsible for the localization of the particular proteins is a protein domain consisting of two α-helices, which we termed V-domain according to the predicted structure. So far we have detected this domain in the following proteins: mammalian BAX, BCL-XL, TCTP and yeast Mmi1p and Erg6p. According to our experiments there are two functions of this domain: (1) shuttling of proteins to mitochondria in times of stress and apoptosis; (2) clearing the outer mitochondrial membrane from pro- as well as anti-apoptotic proteins by moving them to LDs after the stress ceases. In this way the LDs are used by the cell to modulate stress response.

Lipid droplet functions beyond energy storage

“…These changes are prevented in the presence of an autophagy inhibitor, implying that ApoB associated with LDs can also be cleared by lipophagy [175]. Lipophagy has also been implicated in combating ER stress [96] and the removal of unwanted mitochondrial proteins [191]. As elaborated in section 2.2.1, lipid imbalance in budding yeast results in protein misfolding in the ER [192] and the formation of fragmented ER structures that frequently colocalize with LDs [96].…”

“…A similar pathway may also exist for mitochondria. Several proteins normally present in the outer mitochondrial membrane can relocalize to the surface of LDs under certain physiological conditions [191]. In yeast, LDs carrying mitochondrial proteins were observed in the vacuole, hence it was hypothesized that LDs serve as a temporary holding place for such proteins before they, along with the entire LD, are degraded by lipophagy.…”

Mitochatting – If only we could be a fly on the cell wall

“…Recently, the LD-mitochondria contact was suggested to be involved in the regulation of stress responses and apoptosis through a mechanism conserved from yeast to mammals. A special domain termed V-domain was shown to enable the shuttling of pro and antiapoptotic proteins from the outer mitochondrial membrane to LDs, thus allowing modulation of the apoptotic process [137]. Overall it is clear that the mitochondria-LD contact site should be more intensively explored in order to fully grasp the extent of the functions and regulation processes that are occurring within it.…”

Lipid droplet autophagy during energy mobilization lipid homeostasis and protein quality control

“…They also provide support for the model that LDs function as “escape hatches” in ER quality control (86). Interestingly, LDs may also remove damaged proteins from mitochondria in yeast (87). Under conditions of stress, specific damaged mitochondrial outer membrane proteins associate with LDs, which in turn are degraded by lipophagy.…”