Spinal cord injury (SCI) is recognized as a profound traumatic neuropathological condition characterized by extensive neuronal apoptosis, pronounced microglial infiltration and polarization, as well as a marked impairment of motor functions [[1], [2], [3]]. In the wake of such traumatic events, oxidative stress has been identified as a pivotal contributor, precipitating neuronal necrosis through the infliction of damage upon proteins, lipids, and nucleic acids within neurons, ultimately leading to cellular demise [4]. Within this milieu, the role of mitochondrial quality control assumes critical significance as an integral component of the cellular defense mechanism against the onslaught of oxidative stress [5]. Mitochondria, the custodians of metabolic and apoptotic processes, are intricately engaged in a perpetual battle to sustain cellular homeostasis. This is crucial in the neural landscape following SCI, where the equilibrium between mitochondrial biogenesis and degradation is of paramount importance. The preservation of this equilibrium is essential for averting the adverse effects of oxidative stress and maintaining neuronal viability.

Thus, the elucidation of the mechanisms underpinning mitochondrial quality control represents a promising vector for therapeutic intervention. By fortifying the resilience of mitochondria against oxidative stress-induced perturbations, there is potential to mitigate the progression of neuronal loss and ameliorate the functional deficits associated with SCI.

Mitochondrial quality control is a crucial intracellular process involving the regulation of mitochondrial biogenesis, maintenance, and degradation to ensure functional integrity and homeostasis [6,7]. This process is essential for normal cellular function and survival, involving complex interactions among organelles, including ion exchanges between mitochondria and the endoplasmic reticulum, as well as mitophagy between mitochondria and lysosomes [8]. These interactions play a key role in maintaining intracellular stability and mitochondrial function. Previous research has partially revealed the role of mitochondrial quality control in neurological diseases such as optic neuropathy and cerebral ischemia-reperfusion injury [9,10]. These studies not only provide a deeper understanding of the mechanisms of mitochondrial quality control but also offer new insights and directions for developing novel therapeutic approaches.

Lgals3, also known as the anti-cancer protein Galectin-3, is a β-galactoside-binding protein extensively involved in various biological processes such as cell proliferation, differentiation, apoptosis, adhesion, and intercellular interactions. Bax, standing for Bcl2-associated X protein, is a pro-apoptotic protein and a member of the Bcl-2 protein family. Both play critical roles in regulating cellular fate, where Lgals3, through interactions with various intracellular molecules, may influence Bax's activity or distribution, thus participating in the regulation of the apoptotic balance. Understanding the interaction mechanisms between Lgals3 and Bax is significant for in-depth studies of cellular apoptosis progression [11].

The PANoptosis complex stands at the crossroads of various cell death pathways, orchestrating a confluence of processes that include caspase-mediated apoptosis, receptor-interacting protein (RIP)-dependent necroptosis, and Nlrp3 inflammasome-dependent pyroptosis. These pathways are seamlessly integrated with mitochondrial dynamics, with mitochondria serving as a central hub for the regulation and execution of these cell death modalities [[12], [13], [14]]. The complexity of these interactions underscores the mitochondria's role as not only power generators but also as key arbiters of cellular fate. Despite the established connections between mitochondrial functions and PANoptosis, the comprehensive relationship between mitochondrial quality control—encompassing the coordinated regulation of mitochondrial biogenesis, maintenance, and degradation—and PANoptosis remains an area ripe for further investigation [15,16]. As mitochondrial integrity is imperative for cell survival and function, dysregulation of mitochondrial quality control can tip the scales towards cell death, potentially through mechanisms involving the PANoptosis complex. The elucidation of this relationship holds promise for advancing our understanding of the cellular responses to stress and injury, particularly in neurodegenerative diseases and acute brain injuries, where aberrant cell death contributes to disease pathogenesis. Unlocking the mysteries of the interplay between mitochondrial quality control and PANoptosis may reveal novel therapeutic avenues, allowing for targeted interventions to modulate cell death in various pathological conditions.

Zinc, an indispensable trace element, has garnered widespread recognition for its integral role in a plethora of biochemical cascades and critical physiological functions [17]. The burgeoning body of research has progressively shed light on the therapeutic potential of zinc in the context of spinal cord injury (SCI) management [18]. Initial investigations have demonstrated the protective influence of zinc on mitochondrial function, indicating a promising avenue for the development of SCI therapeutics [19,20]. However, a comprehensive elucidation of the mechanisms by which zinc modulates mitochondrial quality control and its consequent effects on SCI treatment remains to be thoroughly expounded. The focus of our study is to meticulously explore the nexus between zinc administration and mitochondrial quality control, with an emphasis on determining how this interaction fortifies neuronal resistance to oxidative stress, thereby curtailing apoptotic pathways following an injurious event. The insights gleaned from our research are expected to significantly contribute to the optimization of zinc-based intervention strategies for SCI and lay the groundwork for further innovative research trajectories.