College of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, PR China; National Engineering Research Center for Miniaturized Detection Systems, Xi'an, Shaanxi, 710069, PR China.
De Duve Institute, Université Catholique de Louvain, Brussels, B-1200, Belgium; Ludwig Institute for Cancer Research, Brussels, B-1200, Belgium.
Redox Biol. 2021 Aug;44:102011. doi: 10.1016/j.redox.2021.102011. Epub 2021 May 20.
Iron deficiency is known to aggravate the prognosis of patients with heart failure. Iron has functions in the mitochondrial respiratory chain. In patients with reduced mitochondrial respiration, the mitochondrial ratio between the level of nicotinamide adenine dinucleotide and its reduced form decreases. Due to the mitochondrial-lysosomal interplay, decreased mitochondrial respiration also leads to inhibition of lysosomal hydrolysis. As a result, cobalamin and iron will be trapped in lysosomes. This will, even if iron and cobalamin have been consumed and absorbed in sufficient amounts, lead to their functional deficiencies. Functional iron deficiency can further impede mitochondrial respiration. Increased plasma levels of methylmalonic acid were shown to predict all-cause and cardiovascular mortality in the general population. Treatments targeting mitochondrial and lysosomal function may correct the functional deficiencies and improve prognosis in a subgroup of patients with heart failure, notably those with skeletal muscle wasting. Methylmalonic acid levels may be used for monitoring response to treatment, thereby identifying patients of the subgroup in which disease outcome may improve.
缺铁已知会加重心力衰竭患者的预后。铁在线粒体呼吸链中具有功能。在线粒体呼吸减少的患者中，烟酰胺腺嘌呤二核苷酸与其还原形式之间的线粒体比率降低。由于线粒体-溶酶体相互作用，线粒体呼吸的减少也会导致溶酶体水解的抑制。结果，钴胺素和铁将被困在溶酶体中。即使铁和钴胺素已经以足够的量被消耗和吸收，这也会导致它们的功能缺陷。功能性缺铁会进一步阻碍线粒体呼吸。研究表明，血浆中甲基丙二酸水平升高可预测一般人群的全因和心血管死亡率。针对线粒体和溶酶体功能的治疗方法可能会纠正功能性缺陷，并改善心力衰竭亚组患者的预后，特别是那些有骨骼肌减少的患者。甲基丙二酸水平可用于监测治疗反应，从而确定疾病结局可能改善的亚组患者。
