Systemic lupus erythematosus (SLE) is a complex autoimmune disease influenced by genetic, environmental, and immunological factors. It is characterized by abnormal B-cell function, autoantibody production and systemic inflammation mediated by immune complexes. The immune system of patients with SLE exerts abnormal attacks on their own tissues, which can affect multiple organs such as the skin, kidneys and heart [1,2]. Epidemiological data show that the global incidence rate of SLE is approximately 1.5–11.0 per 100,000, among which females account for 85 %–95 %. Women of childbearing age (30–50 years old) have a significantly higher risk of developing the disease than men. Moreover, the mortality rate of SLE patients is 2–3 times higher than the general population, with infection and cardiovascular diseases(CVD) are the main causes of death [3,4]. Atherosclerosis(AS) is the main pathological basis of CVD. Research indicates that myocardial infarction in patients with SLE is mainly driven by coronary atherosclerosis, and patients often have vascular diseases in the early stage [5]. In addition to traditional cardiovascular risk factors such as hypertension and hyperlipidemia, non-traditional factors including chronic inflammation and immune cell dysregulation also exacerbate the progression of AS in patients with SLE [6,7]. It is of vital importance to conduct in-depth research on the pathogenic mechanism of AS in patients with SLE.

Mitochondria maintain the balance of cellular energy metabolism by regulating oxidative phosphorylation (OXPHOS) and the tricarboxylic acid cycle (TCA), while serving as the dynamic regulatory center for the generation and clearance of reactive oxygen species (ROS) to sustain the homeostasis redox of the cell [8]. Mitochondrial quality control represents the core mechanism for maintaining mitochondrial homeostasis. It regulates the quantity and functional maturation of mitochondria through mitochondrial biogenesis, modulates the ratio of fission to fusion via mitochondrial dynamics to optimize the mitochondrial network structure, and selectively eliminates mitochondria with oxidative damage or abnormal functions by means of mitophagy [[9], [10], [11]]. In patients with SLE, mitochondrial hyperpolarization in peripheral blood lymphocytes (PBLs) and the consequent ATP depletion render cells more prone to necrosis, which in turn promotes inflammatory responses [12]. Meanwhile, persistent oxidative stress disrupts mitochondrial integrity, promotes the release of mitochondrial DNA (mtDNA) into the cytoplasm, activates the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, and intensifies the type I interferon response [13]. The mitochondrial membrane potential of lymphocyte subsets, single-cell mitochondrial quality, and circulating mtDNA levels can serve as potential diagnostic biomarkers for SLE [14]. Circulating mtDNA in AS can act as a damage-related molecular model, activating the inflammatory response of vascular endothelial cells and macrophages, and thereby promoting plaque progression [15,16]. Moreover, mitophagy dysfunction promotes AS by damaging vascular endothelial cells, inducing abnormal polarization and metabolic disorders of macrophages, and abnormal proliferation and phenotypic transformation of vascular smooth muscle cells [17].

This review focuses on the multi-level mechanisms of mitochondrial dysfunction involved in the development of AS in diverse immune cells and endothelial cells of patients with SLE. By systematically analyzing the interaction network between SLE-related immunometabolic imbalances and mitochondrial dysfunction, the potential mechanism by which mitochondrial dysfunction promotes the pathological process of AS through mediating vascular inflammation, lipid metabolism disorders and oxidative stress cascade reactions is deeply expounded. Meanwhile, it provides a theoretical basis for targeted mitochondrial therapy of SLE complicated by CVD.