Microglial apoptosis is associated with neuroinflammation and no effective strategies are currently available to protect microglia against inflammation-induced apoptosis.Mouse microglial BV-2 cells(5 × 106)were incubated with 10 μg/mL lipopolysaccharides for 12 hours to mimic an inflammatory environment.Then the cells were co-cultured with mitochonic acid 5(MA-5)for another 12 hours.MA-5 improved the survival of lipopolysaccharide-exposed cells.MA-5 decreased the activity of caspase-3,which is associated with apoptosis.MA-5 reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells,and increased adenosine triphosphate levels in cells.MA-5 decreased the open state of the mitochondrial permeability transition pore and reduced calcium overload and diffusion of second mitochondria-derived activator of caspase(Smac).MA-5 decreased the expression of apoptosis-related proteins(mitochondrial Smac,cytoplasmic Smac,pro-caspase-3,cleaved-caspase-3,and caspase-9),and increased the levels of anti-apoptotic proteins(Bcl2 and X-linked inhibitor of apoptosis protein),mitochondria-related proteins(mitochondrial fusion protein 2,mitochondrial microtubule-associated proteins 1A/1B light chain 3B Ⅱ),and autophagy-related proteins(Beclin1,p62 and autophagy related 5).However,MA-5 did not promote mitochondrial homeostasis or decrease microglial apoptosis when Mitofusin 2 expression was silenced.This shows that MA-5 increased Mitofusin 2-related mitophagy,reversed cellular energy production and maintained energy metabolism in BV-2 cells in response to lipopolysaccharide-induced inflammation.These findings indicate that MA-5 may promote the survival of microglial cells via Mitofusin 2-related mitophagy in response to lipopolysaccharide-induced inflammation.