Abstract

   Background: Recent research emphasizes the significant regulatory
   functions of epigenetic alterations and post-translational
   modifications (PTMs) in the ferroptosis process. Despite the existing
   volume of literature, there is a remarkable shortage of comprehensive
   analyses that systematically trace the evolution of research, map key
   investigative routes, evaluate the current situation of the field,
   determine central themes, and predict future directions. This study
   intends to offer a comprehensive summary of the progress achieved
   during the past 12 years in comprehending how epigenetic modifications
   and PTMs regulate ferroptosis.

   Methods: The dataset originated from the Web of Science, covering the
   period from January 1, 2012, to May 21, 2024. By employing advanced
   analytical tools, we carried out an extensive scientometric assessment
   in combination with detailed visual data analysis.

   Results: The results emphasize the crucial role of China, which
   contributes 69.59% of the global research output, thereby demonstrating
   its significant influence on the research trajectory in this domain.
   Remarkable productivity is manifested at institutions such as Central
   South University, Shanghai Jiao Tong University, and Zhejiang
   University. Liu Shuang and Tang Daolin stand out as the most productive
   authors in this field. The journal Cell Death & Disease leads in terms
   of publication volume, having published the greatest number of articles
   related to this area. This study identified hepatocellular carcinoma,
   mitochondrial diseases, and iron overload as the most prominent
   diseases explored in this research domain.

   Conclusion: This meticulous scientometric assessment is beneficial to
   both experienced researchers and newcomers by providing essential
   information and facilitating the derivation of innovative concepts in
   this field.

   Keywords: epigenetics, post-translational modifications, ferroptosis,
   scientometrics, visualization analysis

Introduction

   Ferroptosis, a novel type of programmed cell death (PCD), is marked by
   iron-dependent lipid peroxidation (LPO) of polyunsaturated fatty
   acid-containing phospholipids in cellular membranes[35]^1^-[36]^4. Its
   initiation and implementation are regulated by the equilibrium between
   ferroptosis defense mechanisms[37]^5. The response to ferroptosis
   encompasses various metabolic and degradation pathways that regulate
   LPO or iron accumulation[38]^6. These pathways include lipid, iron, and
   amino acid metabolism, along with degradation mechanisms such as the
   ubiquitin-proteasome system and autophagy. Over the past 12 years,
   research has increasingly associated ferroptosis with the pathogenesis
   of a broad range of diseases, affecting nearly every organ system in
   the body as shown in Figure [39]1[40]^7^, [41]^8. Exploring the
   molecular mechanisms and regulatory pathways of ferroptosis might offer
   novel strategies for treating these conditions.

Figure 1.

   [42]Figure 1
   [43]Open in a new tab

   Ferroptosis markedly influences various systemic disorders, including
   those affecting the nervous, cardiovascular, digestive, respiratory,
   urinary, endocrine systems, among others. This figure was generated
   using Figdraw ([44]https://www.figdraw.com/static/index.html#/).
   Abbreviations: AKI, acute kidney injury; I/R Injury,
   ischemia/reperfusion injury.

   Emerging research suggests precise regulation of ferroptosis at various
   levels, involving both protein post-translational modifications (PTMs)
   and epigenetic alterations[45]^9^, [46]^10. These epigenetic
   mechanisms, including DNA methylation, histone modifications, and
   regulation through noncoding RNAs, provide dynamic and reversible ways
   to control gene expression without altering the DNA
   sequence[47]^11^-[48]^13. PTMs play a vital role in modifying proteins
   via enzymatic or covalent alterations, which affect the localization,
   activity, and interactions at a molecular level[49]^14^, [50]^15. These
   modifications comprise phosphorylation, ubiquitination, SUMOylation,
   and acetylation[51]^15. Abnormal epigenetic changes and PTMs can give
   rise to atypical transcriptional or translational activities, leading
   to drug resistance, cancer progression, metastasis, and other
   pathological conditions. These modifications govern ferroptosis-related
   gene expression, influencing cancer cell susceptibility to ferroptosis
   at both transcriptional and translational stages[52]^9^,
   [53]^16^-[54]^18. Recent studies have emphasized the crucial role of
   epigenetic alterations and PTMs in regulating ferroptosis in various
   medical conditions, including neurological disorders, cardiovascular
   diseases, hepatic conditions, pulmonary disorders, and renal
   diseases[55]^19.

   Science mapping studies often utilize scientometric tools, metrics, and
   indicators to explore scientific literature, identifying and analyzing
   pathways, trends, and theories related to scientific evolution. We
   conducted a comprehensive exploration of how epigenetic modifications
   and PTMs influence ferroptosis, employing both scientometric and
   statistical methods. In contrast to previous traditional
   reviews[56]^10^, [57]^16^, [58]^19^-[59]^27, this article presents
   empirical evidence supported by objective and visual data. This
   considerably reduces the possibility of subjective bias among
   researchers and lowers the degree of variability. This approach
   facilitates a more thorough analysis and helps delineate the current
   research landscape. Furthermore, the study contributes to the existing
   literature by providing an in-depth analysis and visualization of data
   through scientific mapping tools such as CiteSpace and VOSviewer. The
   scientometric analysis indicates both the most and least investigated
   areas in the discipline, identifying topics that require further
   research and suggesting potential collaboration opportunities for
   future research projects. This analysis promotes better communication
   among groups focusing on similar fundamental issues.

   This study aims to explore a set of crucial research questions (RQs)
   designed to enhance our understanding of the field: RQ1: What are the
   dominant trends in recent research on "epigenetic modifications and
   PTMs in ferroptosis"? RQ2: Which countries, institutions, and
   researchers have the most substantial influence in this area of study?
   RQ3: What publications, references, and keywords are most frequently