Brightness and shadows of mitochondrial ROS in the brain

Jimenez-Blasco D, Almeida A, Bolaños JP. Neurobiol Dis. 2023 Aug;184:106199. doi: 10.1016/j.nbd.2023.106199. Epub 2023 Jun PMID: 37321421

Abstract: Mitochondrial reactive oxygen species (mROS) have been generally considered harmful byproducts wanted to clear when elevated to avoid brain damage. However, the abundance of mROS in astrocytes is very high -about one order of magnitude above that in neurons-, despite they are essential to preserve cell metabolism and animal
behavior. Here, we have focused on this apparent ambiguity by discussing (i) the intrinsic mechanisms accounting for the higher production of mROS by the mitochondrial respiratory chain in astrocytes than in neurons, (ii) the specific molecular targets of astrocytic beneficial mROS, and (iii) how decreased astrocytic mROS causes excess neuronal mROS leading to cellular and organismal damage. We hope that this mini-review serves to clarifying the apparent controversy on the beneficial versus deleterious faces of ROS in the brain from molecular to higher-order organismal levels. 

Funding: Authors were supported by the NextGenerationEU/PRTR and Agencia Estatal de Investigacion ´ (10.13039/501100011033; PID2019- 105699RB-I00; PID2022-138813OB-I00; PDC2021–121013-I00; RED2018–102576-T to JPB; RED2022–134407-T to AA); Plan Nacional de Drogas (2020I028 to JPB); Instituto de Salud Carlos III (CB16/10/ 00282 to JPB; PI21/00727; PMP22/00084 and RD21/0006/0005 cofunded by the European Union, to AA); Marie Sklodowska-Curie Action HORIZON-MSCA-2021-DN-01 (101072759 to JPB and AAP), and Junta de Castilla y Leon ´ (CS/151P20 co-funded by P.O. FEDER to AA; Apoyo Regional a la Competitividad Empresarial, ICE 04/18/LE/0017 to JPB, and Escalera de Excelencia CLU-2017-03 to JPB and AA). DJB is a recipient of a Juan de la Cierva-Incorporacion ´ contract(IJC2020–044230-I).