This paper brings a brief review of the human patatin-like phospholipase domain-containing protein (PNPLA) family. Even though it consists of only nine members, their physiological roles and mechanisms of their catalytic activity are not fully understood. However, the results of a number of knock-out and gain- or loss-of-function research models suggest that these enzymes have an important role in maintaining the homeostasis and integrity of organelle membranes, in cell growth, signalling, cell death, and the metabolism of lipids such as triacylglycerol, phospholipids, ceramides, and retinyl esters. Research has also revealed a connection between PNPLA family member mutations or irregular catalytic activity and the development of various diseases. Here we summarise important findings published so far and discuss their structure, localisation in the cell, distribution in the tissues, specificity for substrates, and their potential physiological role, especially in view of their potential as drug targets.
Ovaj revijalni rad donosi pregled dosadašnjih spoznaja o porodici PNPLA (engl. patatin-like phospholipase domain-containing proteins) ljudskih enzima. Iako ovu porodicu čini samo 9 članova, najmanji sadrži 253 aminokiseline, a najveći više od 1360 aminokiselina, fiziološka uloga i mehanizam katalitičke aktivnosti nisu do sada potpuno razriješeni niti za jednoga. Međutim, rezultati brojnih tzv. knock-out, gain-of-function i loss-of-function modela istraživanja upućuju na važnu ulogu ovih enzima u mnogim biološkim procesima, uključujući održavanje homeostaze i integriteta stanične membrane, rast stanice, staničnu signalizaciju, staničnu smrt i metabolizam lipida kao triacilglicerola, fosfolipida, ceramida i retinil estera. Također, rezultati istraživanja upozoravaju na povezanost mutacija i nepravilne aktivnosti pojedinih članova s razvojem raznih bolesti. Radi boljeg razumijevanja PNPLA porodice enzima i naglaska na njihov potencijal kao mete razvoja novih lijekova, donosimo sveobuhvatni pregled do sada poznatih spoznaja koje uključuju strukturu, lokalizaciju u stanici, distribuciju u tkivima, specifičnost prema supstratima i potencijalnu fiziološku ulogu.
Keywords: catalytic dyad; fosfolipaze; katalitička dijada; lipid droplets; lipidne kapljice; patatin; phospholipases; serine hydrolases; serinske hidrolaze.
© 2023 Ana-Marija Lulić et al., published by Sciendo.