It has been an honor to edit this special issue on the ‘Cell Biology of Mitochondria’ for Journal of Cell Science (JCS). The impact of mitochondrial research on all fields of biomedical sciences continues to grow as new discoveries open unexpected pathways at a rapid pace. Far beyond their roles as simply the energy powerhouse of the cell, mitochondria have emerged as central players within cellular pathways, with new studies highlighting their mechanisms of dynamic metabolic wiring, their integration within cell signaling pathways, their biogenesis and turnover pathways, and the fundamental mechanisms that govern mitochondrial dynamics. It is an exciting time for the field, especially as many of these processes have become more tightly linked to disease pathways and tissue-specific behaviors.
This special issue contains a series of articles that touch on these exciting themes. Given the strong focus in the field on quality control mechanisms, the issue includes several studies on this topic, including articles examining mitophagy pathways during ischemia–reperfusion (Nàger et al., 2025), and irradiation-induced alterations in mitochondrial dynamics and mtDNA removal (Buckley et al., 2025). Quality control at the import translocon is also highlighted in an ‘Cell Science at a Glance’ poster article (Balzarini et al., 2025). Links between the mitochondria unfolded protein response and generation of stress granules are also revealed (Lopez-Nieto et al., 2025), along with new work exploring how manipulating translation under oxidative and nutritional stress affects the dynamic assembly of the mRNA-binding protein Clu into particles regulation mitochondrial protein synthesis (Hwang et al., 2025).
Focusing on the regulation of import and cristae architecture, new studies identify novel TOM complex interactors (Özdemir et al., 2025), roles of the outer membrane proteins Miro and metaxin proteins in cristae organization (Shembekar et al., 2025), and exciting new biology behind intermembrane space redox-regulated Mia40 pathways (Resch et al., 2025). Miro1 is also examined in the context of ERK signaling and cell cycle progression (Shannon et al., 2025), providing further insight into the integration of mitochondrial signaling with cell fate decisions. The identification of the C. elegans ortholog of PPARδ, termed NHR-85, whose disruption is demonstrated to regulate mitochondrial metabolism, reducing mitophagy and increasing aggregation of α-synuclein, provides a new model relevant to work in Parkinson's disease and the impact of mitochondrial function (Tsagkari et al., 2025). A further paper links mitochondrial function to cell migration pathways (Pacheco et al., 2025), and two new contributions also focus on metabolic wiring through the TCA cycle with new approaches to reduce succinate accumulation in adrenal cells (Al Khazal et al., 2025) and how pyruvate and uridine can prevent hypertrophy in multiple systems (Mukherjee et al., 2025).
Lipid metabolism lies at the center of mitochondrial cell biology and inter-organellar contact sites, including in pathways revealed within this special issue. The role of ERMES-regulated contact sites in drug sensitivity and virulence of fungal infections are explored (Kumari et al., 2025), new mechanisms that define the dynamic regulation of mitochondria to plasma membrane versus ER contacts are described (Casler et al., 2025) and the role of OCIAD in mitochondria-peroxisome contacts in lipid metabolism is uncovered (Linke et al., 2025). The revolution in cryo-EM reconstruction approaches continues here with a new study that provides stunning images and insight into mitochondrial fission events, highlighting ER contacts and surrounding organelles (Kirchweger et al., 2025). A summary of the current status of knowledge on contact sites is also highlighted in another Cell Science at a Glance poster (Diokmetzidou and Scorrano, 2025), while new methodology is described to generate an inventory of mitochondrial proteins, lipids and metabolites in a Tools and Resources article (Cunningham et al., 2025).
The front section of the issue is full of insightful and timely discussions on distinct aspects of the field, from cholesterol transit through mitochondria (Simmen and Pellegrini, 2025), to our progress in mitochondrial fission (Kamerkar et al., 2025) and mitochondrial gene expression in the regulation of cellular communication (Zilio et al., 2025). At the broadest level, an Opinion highlights mitochondria as the ‘Chief Executive Organelle’ (CEO) of the cell (Lee-Glover et al., 2025). We are also taken back to the beginning of time with an updated evolutionary perspective on mitochondrial biology (Venkatraman et al., 2025). Finally, no issue of JCS is complete without highlighting some of the exciting scientists behind the greatest new discoveries in the field to inspire the next generation. Here, we enjoy interviews with Tom MacVicar (doi:10.1242/jcs.263978) and Sam Lewis (doi:10.1242/jcs.264065), two trail blazers who share their vision of the field and their future work.
We are very grateful to the authors who submitted their work for review, and to the reviewers who dedicated their time to provide thoughtful and constructive feedback throughout. The articles included highlight the important work going on in this field from so many diverse angles and model systems that take innovative approaches. We hope this issue will help promote JCS as a home for mitochondrial science. The editorial staff and leadership at the journal have been a joy to work with, and their dedication to enhance the publishing landscape by supporting scientists across disciplines, countries and stages, is truly awe inspiring. We are grateful for their support and guidance throughout this experience.
In conclusion, the field of mitochondrial biology has gone through many distinct stages where major advances have continued to take the field by surprise. Often underestimated, the secrets of mitochondria never cease to amaze. From the earliest documentation of mitochondrial dynamics by Margaret Lewis in 1915 (Lewis and Lewis, 1915), through the long debates on chemiosmotic theory (Mitchell and Moyle, 1967; Slater, 1967) and evolutionary origins through the 1950–1980s (Lazcano and Pereto, 2021), and to controversies on mitochondria in cell death through the 1990s (Susin et al., 1998), our field has been defined by major conceptual leaps that teach us how mitochondria are integrated within, and drive, cellular pathways. There is so much left to learn as these conceptual advances continue unabated. The recent explosion of work on the mechanisms of mtDNA release, something few of us would ever have anticipated, has offered crucial insights into mitochondrial signaling in immune and other pathways (VanPortfliet et al., 2024). Studies on mitochondrial transfer between cells are also pushing into new areas of biology (Brestoff et al., 2025), but our mechanistic understanding of these pathways is only just beginning. These, and other pathways, are ripe for investigation and careful cell biological approaches that are essential to get these concepts into the clinic. As long-standing ‘mitochondriaks’, we are thrilled to highlight our field to the broad readership of JCS. We hope you enjoy reading the special issue and hope you will consider JCS as a welcoming home for your next article on this topic.
