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Background informationPoly(ADP‐ribose) Polymerase‐1 (PARP‐1) is predominantly a nuclear protein and involved in various cellular processes like DNA repair, cell death, development, chromatin modulation etc. PARP‐1 utilizes NAD+ and adds negatively charged PAR moieties on the target proteins. Over‐activation of PARP‐1 has been shown to cause energy crisis mediated cell death in which mitochondrial homeostasis is also affected. Moreover, the presence of mitochondrial NAD+ pools highlights the role of PARP‐1 in mitochondria. The aim of present study is to understand the physiological role of PARP‐1 in regulating mitochondrial functioning by varying the levels of PARP‐1 in Dictyostelium discoideum. Intra‐mitochondrial PARylation was analyzed by indirect immunofluorescence. Further, the effect of altered levels of PARP‐1 i.e. overexpression, downregulation, knockout and its chemical inhibition was studied on mitochondrial respiration, reactive oxygen species (ROS) levels, ATP production, mitochondrial fission‐fusion, mitochondrial morphology and mitochondrial DNA (mtDNA) content of D. discoideum.ResultsOur results show intra‐mitochondrial PARylation under oxidative stress. Altered levels of PARP‐1 caused impairment in the mitochondrial respiratory capacity, leading to elevated ROS levels and reduced ATP production. Moreover, PARP‐1 affects the mitochondrial morphology and mtDNA content, alters the mitochondrial fission‐fusion processes in lieu of preventing cell death under physiological conditions.ConclusionThe current study highlights the physiological role of PARP‐1 in mitochondrial respiration, its morphology, fission‐fusion processes and mtDNA maintenance in D. discoideum.SignificanceThis study would provide new clues on the PARP‐1's crucial role in mitochondrial homeostasis, exploring the therapeutic potential of PARP‐1 in various mitochondrial diseases.